PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 19755425-5 2009 Surprisingly, inhibition of the mTOR protein complex 1 (mTORC1) with rapamycin did not impair LTP maintenance or Arc synthesis nor did it inhibit eIF4F formation or phosphorylation of eIF4E. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 56-62 19692352-6 2009 Furthermore, cyst development requires mTORC1 activation, as low dosage of rapamycin administration effectively blocks cyst formation. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 39-45 19901542-4 2009 Recent insights now indicate that rapamycin is a partial inhibitor of mTOR through allosteric inhibition of mTOR complex-1 (mTORC1) but not mTOR complex-2 (mTORC2). Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 124-130 19963098-2 2009 mTOR is found in two different complexes within the cell, mTORC1 and mTORC2, but only mTORC1 is sensitive to inhibition by rapamycin. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 86-92 19783659-10 2009 Rapamycin modifies the hepatic AADR to asparaginase by preventing CHOP induction while maximizing inhibition of mTORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 112-118 19729590-9 2009 Taken together, these findings indicate that in vivo insulin resistance can occur without an increase in mTORC1 activity in skeletal muscle and that inhibition of mTORC1 with rapamycin does not improve insulin action. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 163-169 19718660-7 2009 Cancer cells have a constitutively active mTOR pathway; surprisingly, inhibition of mTOR complex 1 (mTORC1) by rapamycin barely affects the global rate of translation and of initiation of translation, but deeply inhibits mesothelioma spreading on ECM. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 100-106 19131641-3 2009 To examine these issues, we determined the effects of rapamycin-induced inhibition of mTORC1 on TLR2- and TLR4-induced neutrophil activation. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 86-92 19771169-9 2009 By contrast, transient exposure to the mTORC1 inhibitor rapamycin caused essentially irreversible mTORC1 inhibition, sustained inhibition of cell growth and no selective cell killing in starvation. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 39-45 19771169-9 2009 By contrast, transient exposure to the mTORC1 inhibitor rapamycin caused essentially irreversible mTORC1 inhibition, sustained inhibition of cell growth and no selective cell killing in starvation. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 98-104 19720745-4 2009 We find that one site, T1135, undergoes growth factor-responsive phosphorylation that is acutely sensitive to rapamycin and is phosphorylated downstream of mTORC1. Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 156-162 19564418-1 2009 Rapamycin, a selective inhibitor of mTORC1 signaling, blocks terminal myoblast differentiation. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 36-42 19564418-4 2009 Importantly, downregulation of rictor inhibited TORC2 signaling without inhibiting mTORC1 signaling, suggesting that inhibition of mTORC1 by rapamycin may not be the cause of arrested differentiation. Sirolimus 141-150 CREB regulated transcription coactivator 1 Mus musculus 131-137 19443844-8 2009 Rapamycin decreased phosphorylation of both Akt and S6, suggesting that both the TORC1 and TORC2 pathways are impacted. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 81-86 19188252-2 2009 In an effort to determine whether mTORC1 signalling is essential for regulating muscle protein synthesis in humans, we treated subjects with a potent mTORC1 inhibitor (rapamycin) prior to performing a series of high-intensity muscle contractions. Sirolimus 168-177 CREB regulated transcription coactivator 1 Mus musculus 150-156 19541609-4 2009 Consistent with a central role for mTORC1 in these tumors, rapamycin as a single agent results in a dramatic suppression of preexisting GI polyps in LKB1+/- mice. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 35-41 19245654-4 2009 Recent work has revealed that across eukaryotes mTOR orthologues are found in two biochemically distinct complexes and only one of those complexes (mTORC1 in mammals) is acutely sensitive to rapamycin and regulated by nutrients and AMPK. Sirolimus 191-200 CREB regulated transcription coactivator 1 Mus musculus 148-154 19297407-3 2009 The gene products of TSC1 and TSC2, also known as hamartin and tuberin, respectively, form a physical and functional complex and inhibit the mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 182-188 19270529-5 2009 Second, the efficacy of rapamycin is dependent on the level of phosphatidic acid (PA), which is required for the assembly of both mTORC1 and mTORC2 complexes. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 130-136 19372588-3 2009 In contrast, treatment of melanoma with the pan-class I PI3K inhibitor ZSTK474 or the mTORC1 inhibitor rapamycin resulted only in minor reduction of cell proliferation. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 86-92 19451225-8 2009 In conclusion, the deregulation of mTORC1 activation underlies the aberrant growth and proliferation of NF2-associated tumors and may restrain the growth of these lesions through negative feedback mechanisms, suggesting that rapamycin in combination with phosphoinositide 3-kinase inhibitors may be therapeutic for NF2. Sirolimus 225-234 CREB regulated transcription coactivator 1 Mus musculus 35-41 19379082-4 2009 However, in recent preclinical studies a sustained exposure of cancer cells to rapamycin has been shown to inhibit the function of both mTORC1 and mTORC2 complexes. Sirolimus 79-88 CREB regulated transcription coactivator 1 Mus musculus 136-142 19188252-4 2009 In addition, several downstream components of the mTORC1 signalling pathway were also blunted or blocked by rapamycin. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 50-56 19188252-7 2009 Rapamycin administration prior to exercise also reduced the ability of raptor to associate with mTORC1 during post-exercise recovery. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 96-102 19200882-3 2009 mTORC1 activity is inhibited by rapamycin, a specific inhibitor of mTOR, whereas mTORC2 activity is resistant to short-term treatments with rapamycin. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 0-6 19197153-2 2009 Rapamycin, an allosteric inhibitor of mTORC1, has been approved for treatment against renal cell carcinomas and is being evaluated for other cancers. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 38-44 19211884-6 2009 Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1), can prevent and reverse neuronal hypertrophy, resulting in the amelioration of a subset of PTEN-associated abnormal behaviors, providing evidence that the mTORC1 pathway downstream of PTEN is critical for this complex phenotype. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 97-103 19211884-6 2009 Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1), can prevent and reverse neuronal hypertrophy, resulting in the amelioration of a subset of PTEN-associated abnormal behaviors, providing evidence that the mTORC1 pathway downstream of PTEN is critical for this complex phenotype. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 261-267 19143643-5 2009 Phase I/II clinical trials of the mTORC1 inhibitor rapamycin have demonstrated reduction in size of tuberous-sclerosis- and LAM-associated renal tumours (angiomyolipomas) and some evidence for reversible improvement in lung function in patients with LAM. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 34-40 19150980-2 2009 Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppressant and anti-cancer agent. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 33-39 19150980-6 2009 Our findings challenge the assumption that rapamycin completely inhibits mTORC1 and indicate that direct inhibitors of mTORC1 kinase activity may be more successful than rapamycin at inhibiting tumors that depend on mTORC1. Sirolimus 43-52 CREB regulated transcription coactivator 1 Mus musculus 73-79 19114562-0 2009 Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 14-20 19114562-9 2009 Data provided here demonstrate a PA requirement for the stabilization of both mTORC1 and mTORC2 complexes and reveal a mechanism for the inhibitory effect of rapamycin on mTOR. Sirolimus 158-167 CREB regulated transcription coactivator 1 Mus musculus 78-84 19074679-9 2009 Therefore, other mTORC1 targets are more important in the inhibition by rapamycin of the rapid activation of protein synthesis and of cell growth. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 17-23 18945681-5 2008 mTOR exists in two complexes, mTORC1 and mTORC2, which are differentially sensitive to rapamycin. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 30-36 19305497-8 2009 Inhibition of mTORC1 by rapamycin did not affect proinsulin and total protein synthesis in beta-cells incubated at high glucose with palmitate. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 19018001-4 2008 We found that rapamycin, which blocks mTORC1 and mTORC2 signaling, inhibited sCD40L-mediated transactivation of VEGF. Sirolimus 14-23 CREB regulated transcription coactivator 1 Mus musculus 38-44 18832178-5 2008 mTORC1 activation by SF2/ASF bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF-mediated transformation, as inhibition of mTOR by rapamycin blocked transformation by SF2/ASF in vitro and in vivo. Sirolimus 145-154 CREB regulated transcription coactivator 1 Mus musculus 0-6 18776922-6 2008 Inhibition of both mTORC1 and mTORC2 by rapamycin-induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 19-25 18812319-2 2008 mTOR forms two functionally distinct complexes, termed the mTOR complex 1 (mTORC1) and 2 (mTORC2); only the former of which is inhibited by rapamycin. Sirolimus 140-149 CREB regulated transcription coactivator 1 Mus musculus 75-81 19100909-7 2008 Mammalian TORC1 (mTORC1) is rapamycin sensitive and contains mTOR, raptor, and mLST8. Sirolimus 28-37 CREB regulated transcription coactivator 1 Mus musculus 17-23 18776922-8 2008 These results indicate the presence of two parallel cell-survival pathways in prostate cancer cells: a strong Akt-independent, but rapamycin-sensitive pathway downstream of mTORC1, and an AR-dependent pathway downstream of mTORC2 and Akt, that is stimulated by mTORC1 inhibition. Sirolimus 131-140 CREB regulated transcription coactivator 1 Mus musculus 173-179 18955708-3 2008 It is generally accepted that rapamycin, a specific inhibitor of mTORC1, is a potent translational repressor. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 65-71 18621930-3 2008 Since mTORC1 regulates growth, we hypothesized that pharmacological inhibition of mTORC1 by rapamycin may reverse the phenotypic effects of c-MYC. Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 6-12 18614546-0 2008 Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Sirolimus 81-90 CREB regulated transcription coactivator 1 Mus musculus 62-68 18621930-3 2008 Since mTORC1 regulates growth, we hypothesized that pharmacological inhibition of mTORC1 by rapamycin may reverse the phenotypic effects of c-MYC. Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 82-88 18722121-9 2008 CONCLUSIONS: We propose a unique mode of mTOR regulation in which RSK-mediated phosphorylation of Raptor regulates mTORC1 activity and thus suggest a means by which the Ras/MAPK pathway might promote rapamycin-sensitive signaling independently of the PI3K/Akt pathway. Sirolimus 200-209 CREB regulated transcription coactivator 1 Mus musculus 115-121 18762023-4 2008 Furthermore, nuclear accumulation of the mature form of the sterol responsive element binding protein (SREBP1) and expression of SREBP target genes was blocked by the mTORC1 inhibitor rapamycin. Sirolimus 184-193 CREB regulated transcription coactivator 1 Mus musculus 167-173 18587048-10 2008 The reduction of beta cell mass in betaTsc2(-/-) mice by inhibition of the mTOR/Raptor (TORC1) complex with rapamycin treatment suggests that TORC1 mediates proliferative and growth signals induced by deletion of Tsc2 in beta cells. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 88-93 18725988-6 2008 Significantly, pharmacological inhibition of the MAPK pathway enhanced the antitumoral effect of mTORC1 inhibition by rapamycin in cancer cells in vitro and in a xenograft mouse model. Sirolimus 118-127 CREB regulated transcription coactivator 1 Mus musculus 97-103 18664580-5 2008 Tumors from Tsc2(+/-)E mu-Myc mice underwent rapid apoptosis upon blockade of mTORC1 by rapamycin. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 78-84 18587048-10 2008 The reduction of beta cell mass in betaTsc2(-/-) mice by inhibition of the mTOR/Raptor (TORC1) complex with rapamycin treatment suggests that TORC1 mediates proliferative and growth signals induced by deletion of Tsc2 in beta cells. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 142-147 18025151-6 2008 Rapamycin inhibited mTORC1 signaling and suppressed CTCL cell proliferation but showed little effect on their apoptotic rate when used as a single agent. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 20-26 18303120-6 2008 Treatment with rapamycin [a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1)] inhibited the increased PTEN expression and partially restored insulin-stimulated glucose transport and Akt activation to insulin-resistant cells. Sirolimus 15-24 CREB regulated transcription coactivator 1 Mus musculus 91-97 18354181-5 2008 Rapamycin, a specific inhibitor of mTORC1, selectively and completely blocked the FcepsilonRI- and Kit-induced mTORC1-dependent p70S6K phosphorylation and partially blocked the 4E-BP1 phosphorylation. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 35-41 18354181-5 2008 Rapamycin, a specific inhibitor of mTORC1, selectively and completely blocked the FcepsilonRI- and Kit-induced mTORC1-dependent p70S6K phosphorylation and partially blocked the 4E-BP1 phosphorylation. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 111-117 18250144-7 2008 Under the conditions adopted, rapamycin inhibited both mammalian target-of-rapamycin complexes (mTORC1 and mTORC2), as indicated by the reduced amount of raptor and rictor bound to mTOR in immunoprecipitates and by the marked hypophosphorylation of protein S6 kinase I (p70S6K) and Akt, determined by western blotting. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 96-102 18495876-9 2008 Strikingly, mice treated with rapamycin or RAD001 for 23 d only (postnatal days 7-30) displayed a persistent improvement in phenotype, with median survival of 78 d. In summary, rapamycin/RAD001 are highly effective therapies for this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 and Akt signaling and, consequently, cell size and myelination. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 308-314 18495876-9 2008 Strikingly, mice treated with rapamycin or RAD001 for 23 d only (postnatal days 7-30) displayed a persistent improvement in phenotype, with median survival of 78 d. In summary, rapamycin/RAD001 are highly effective therapies for this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 and Akt signaling and, consequently, cell size and myelination. Sirolimus 177-186 CREB regulated transcription coactivator 1 Mus musculus 308-314 17971516-11 2008 Rapamycin inhibited TNF-alpha-induced phosphorylation of the mTOR C1 target p70(S6K) without altering TNF-alpha-induced PS and 4E-BP1 phosphorylation. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 61-68 17656678-5 2007 Our work establishes an immunologic stimulus for mTORC1 signaling in vascular smooth muscle cells, emphasizes that mTORC1 activation is critical in immune-mediated vascular remodeling, and provides further mechanistic insight into the successful clinical application of rapamycin therapy for atherosclerosis and graft arteriosclerosis. Sirolimus 270-279 CREB regulated transcription coactivator 1 Mus musculus 49-55 18556237-5 2008 Stimulation of eIF2Bepsilon translation was reversed by pre-treatment with the mTORC1 inhibitor rapamycin. Sirolimus 96-105 CREB regulated transcription coactivator 1 Mus musculus 79-85 17656678-5 2007 Our work establishes an immunologic stimulus for mTORC1 signaling in vascular smooth muscle cells, emphasizes that mTORC1 activation is critical in immune-mediated vascular remodeling, and provides further mechanistic insight into the successful clinical application of rapamycin therapy for atherosclerosis and graft arteriosclerosis. Sirolimus 270-279 CREB regulated transcription coactivator 1 Mus musculus 115-121 17334390-1 2007 Rapamycin, a natural product inhibitor of the Raptor-mammalian target of rapamycin complex (mTORC1), is known to induce Protein kinase B (Akt/PKB) Ser-473 phosphorylation in a subset of human cancer cell lines through inactivation of S6K1, stabilization of insulin receptor substrate (IRS)-1, and increased signaling through the insulin/insulin-like growth factor-I/phosphatidylinositol 3-kinase (PI3K) axis. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 92-98 17052453-4 2006 In these settings, GSK3 phosphorylation is sensitive to mTORC1 inhibition by rapamycin or amino acid withdrawal, and GSK3 becomes a direct target of S6K1. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 56-62 17568186-8 2007 The addition of rapamycin, an inhibitor of mTORC1, diminished the remaining activity of mTORC1 and significantly intensified the cytotoxic action of cisplatin in AFPGC cells. Sirolimus 16-25 CREB regulated transcription coactivator 1 Mus musculus 43-49 17568186-8 2007 The addition of rapamycin, an inhibitor of mTORC1, diminished the remaining activity of mTORC1 and significantly intensified the cytotoxic action of cisplatin in AFPGC cells. Sirolimus 16-25 CREB regulated transcription coactivator 1 Mus musculus 88-94 17407584-8 2007 CONCLUSION: The sensitivity of HTLV-I transcription to rapamycin may be effected through an NF-kappaB-pathway associated with the rapamycin-sensitive mTORC1 cellular signalling network. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 150-156 17234746-6 2007 Furthermore, depletion of PATJ from Caco2 cells induces an increase in mammalian Target Of Rapamycin Complex 1 (mTORC1) activity, which is totally inhibited by rapamycin. Sirolimus 160-169 CREB regulated transcription coactivator 1 Mus musculus 112-118 33942341-1 2021 AIMS: Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signalling pathway. Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 141-147 16870609-3 2006 mTORC1 (mTOR complex 1) is rapamycin-sensitive and regulates the rate of protein synthesis in part by phosphorylating two well established effectors, S6K1 (p70 ribosomal S6 kinase 1) and 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1). Sirolimus 27-36 CREB regulated transcription coactivator 1 Mus musculus 0-6 33800501-3 2021 Thus, the critical roles of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) pathway and its regulators are reviewed. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 81-87 33761878-10 2021 The interaction of mitochondrial genotype (mtDNA) with rapamycin treatment identifies new links between mitochondria and the nutrient-sensing mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 142-148 33762334-5 2021 Adipocyte leptin was regulated by the mechanistic target of rapamycin complex 1 (mTORC1) and blocked by rapamycin. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 81-87 33802760-4 2021 We have previously reported that the Ras homolog protein enriched in brain (Rheb)-mammalian target of rapamycin complex 1 (mTORC1) axis plays a vital role in preventing neuronal death in the brain of AD and PD patients. Sirolimus 102-111 CREB regulated transcription coactivator 1 Mus musculus 123-129 33804169-6 2021 We find that within GBM cells, radiation exposure induces DYRK3 expression and DYRK3 regulates mammalian target of rapamycin complex 1 (mTORC1) activity through phosphorylation of proline-rich AKT1 substrate 1 (PRAS40). Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 136-142 33803410-2 2021 Recent epidemiological studies associate the intake of cow"s milk with an increased risk of diseases, which are associated with overactivated mechanistic target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 164-173 CREB regulated transcription coactivator 1 Mus musculus 185-191 32796887-2 2020 Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular functions such as proliferation and autophagy by various external stimuli. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 41-47 33778324-3 2021 In addition, we showed that resveratrol reduces mammalian target of rapamycin complex 1 (mTORC1) signaling, suggesting a potential mechanism. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 89-95 33234350-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) is a central modulator of inflammation and tumorigenesis in the gastrointestinal tract. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 25548282-10 2015 mTORC1 inhibition, by treatment with rapamycin, reversed changes in autophagic flux, and cell death induced by glucose/PA. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 0-6 25574706-6 2015 Interestingly, inhibition of hypothalamic mTORC1 with rapamycin reversed the food intake- and body weight-lowering effects of ICV insulin. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 42-48 26220174-4 2015 To study the effects of mTORC1 activation on mitochondrial structure and function, mTORC1 was inhibited by treating Acsl1(T-/-) and littermate control mice with rapamycin or vehicle alone for 2 wk. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 83-89 34191518-5 2022 Our studies showed that WRX606 formed a ternary complex with FK506-binding protein-12 (FKBP12) and FKBP-rapamycin-binding (FRB) domain of mTOR, resulting in the allosteric inhibition of mTORC1. Sirolimus 104-113 CREB regulated transcription coactivator 1 Mus musculus 186-192 34977370-9 2022 In summary, our results indicated that glycine alleviates ER stress-induced apoptosis and intestinal barrier dysfunction in IPEC-1 cells in a mammalian target of rapamycin complex 1 (mTORC1)-dependent manner. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 183-189 34932133-9 2022 Of note, aripiprazole increased beta cell size (p<0.05) and mass (p<0.01) vs mice fed a control chow diet, along with activation of mechanistic target of rapamycin complex 1 (mTORC1)/S6 signalling, without preventing beta cell dysfunction. Sirolimus 154-163 CREB regulated transcription coactivator 1 Mus musculus 175-181 23888043-0 2013 mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 0-6 23888043-1 2013 The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) protein kinase promotes growth and is the target of rapamycin, a clinically useful drug that also prolongs life span in model organisms. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 54-60 23888043-2 2013 A persistent mystery is why the phosphorylation of many bona fide mTORC1 substrates is resistant to rapamycin. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 66-72 23888043-4 2013 Slight modifications of the sites were sufficient to alter mTORC1 activity toward them in vitro and to cause concomitant changes within cells in their sensitivity to rapamycin and starvation. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 59-65 34963894-7 2021 Importantly, lysosomal 3-PIs are needed for growth-factor-induced activities of Akt and mechanistic target of rapamycin complex 1 (mTORC1) on the lysosomal surface, as targeted depletion of 3-PIs has detrimental effects. Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 131-137 34779571-6 2022 Loss of genes belonging to von Hippel-Lindau (VHL) and mammalian target of rapamycin complex 1 (mTORC1) pathways caused resistance to acute IMT1 treatment and the relevance of these pathways was confirmed by chemical modulation. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 96-102 34852208-1 2022 Following anabolic stimuli (mechanical loading and/or amino acid provision) the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of protein synthesis, translocates toward the cell periphery. Sirolimus 102-111 CREB regulated transcription coactivator 1 Mus musculus 123-129 34968488-2 2022 Numerous previous studies have shown the role of central mammalian target of rapamycin complex 1 (mTORC1) signaling in depression. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 98-104 34905649-8 2022 Mechanistically, GDF11 significantly activates mammalian target of rapamycin complex 1 (mTORC1) and subsequently represses transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 88-94 34972198-6 2021 Deletion of the gene encoding the GTPase RHE2, whose mammalian orthologue activates mTORC1, led to rapamycin hypersensitivity and altered secondary metabolism, but had an only minor effect on vegetative growth and mycoparasitic overgrowth. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 84-90 34941873-8 2021 Inhibition of mTORC1 by rapamycin rescues the hepatomegaly and liver dysfunction of lvh. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 34987410-1 2021 Background: The mechanistic target of rapamycin complex 1 (mTORC1) signaling has served as a promising target for therapeutic intervention of major depressive disorder (MDD), but the mTORC1 signaling underlying MDD has not been well elucidated. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 59-65 34927743-2 2021 5"-Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor suppressing mammalian target of rapamycin complex 1 (mTORC1) activity. Sirolimus 121-130 CREB regulated transcription coactivator 1 Mus musculus 142-148 34089815-9 2021 The antidepressant-like and pro-synaptogenic effects elicited by ketamine plus guanosine were abolished by the pretreatment with rapamycin (0.2 nmol/site, i.c.v., a selective mTORC1 inhibitor). Sirolimus 129-138 CREB regulated transcription coactivator 1 Mus musculus 175-181 34839600-8 2021 After 30 min of culture, phosphorylation level of mammalian target of rapamycin complex 1 (mTORC1), p70 ribosomal protein S6 kinase (P70 S6k), and eIF4E-binding protein 1 (4E-BP1) were detected by Western blotting. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 91-97 34987410-1 2021 Background: The mechanistic target of rapamycin complex 1 (mTORC1) signaling has served as a promising target for therapeutic intervention of major depressive disorder (MDD), but the mTORC1 signaling underlying MDD has not been well elucidated. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 183-189 34976315-3 2022 Lack of nutrients or the presence of stress leads to downregulation of ribosome biogenesis, a process for which mechanistic target of rapamycin complex I (mTORC1) is key. Sirolimus 134-143 CREB regulated transcription coactivator 1 Mus musculus 155-161 34944053-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) has been linked to different diseases. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 34959437-1 2021 The inhibition of the mammalian target of rapamycin complex 1 (mTORC1) by everolimus (RAD001) was recently shown to enhance the tumor uptake of radiolabeled minigastrin. Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 63-69 34941746-6 2021 IS also induced epithelial-mesenchymal transition of tubular epithelial cells (HK-2 cells), differentiation of fibroblasts into myofibroblasts (NRK-49F cells), and inflammatory response of macrophages (THP-1 cells), which are associated with renal fibrosis, and these effects were inhibited in the presence of rapamycin (mTORC1 inhibitor). Sirolimus 310-319 CREB regulated transcription coactivator 1 Mus musculus 321-327 34941746-8 2021 The administration of AST-120 or rapamycin targeted to IS or mTORC1 ameliorated renal fibrosis in Adenine-induced CKD mice. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 61-67 34878722-3 2022 Mechanistic target of rapamycin complex 1 (mTORC1) is known to control fundamental processes in ageing: inhibiting this signalling complex slows biological ageing, reduces age-related disease pathology, and increases lifespan in model organisms. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 34673573-2 2021 To identify the molecular underpinnings of this phenotype, we analyzed a large cohort of MBs developing in p53-deficient Ptch+/- SHH mice that, unexpectedly, showed LC/A traits that correlated with mechanistic Target Of Rapamycin Complex 1 (mTORC1) hyperactivation. Sirolimus 220-229 CREB regulated transcription coactivator 1 Mus musculus 241-247 34563639-1 2021 Inhibition of mammalian target of rapamycin complex 1 (mTORC1) with rapamycin in the absence of transforming growth factor-beta (TGFbeta) signaling induces apoptosis in many cancer cell lines. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 55-61 34938782-8 2021 Besides, HCP1 activated the activity of mechanistic target of rapamycin complex 1 (mTORC1), co-treatment with AMPK activator acadesine eliminated the effect of HCP1 on mTORC1 activity as well as autophagy. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 83-89 34862383-1 2021 Amino acid availability is sensed by various signaling molecules, including general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 144-153 CREB regulated transcription coactivator 1 Mus musculus 165-171 34944458-4 2021 Interestingly, both wild-type DGKbeta and the kinase-negative (KN) mutant partially induced neurite outgrowth, and these functions shared a common pathway via the activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 197-206 CREB regulated transcription coactivator 1 Mus musculus 218-224 34738031-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) integrates various types of signal inputs, such as energy, growth factors, and amino acids to regulate cell growth and proliferation mainly through the 2 direct downstream targets, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1). Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34365025-4 2021 Herein, we report that constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling via Tsc1 (Tuberous sclerosis 1) deletion in chondrocytes causes abnormal skull development with decreased size and rounded shape. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 97-103 34365025-9 2021 Lastly, treatment with rapamycin, an inhibitor of mTORC1, rescued the abnormality in synchondroses. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 50-56 34563639-1 2021 Inhibition of mammalian target of rapamycin complex 1 (mTORC1) with rapamycin in the absence of transforming growth factor-beta (TGFbeta) signaling induces apoptosis in many cancer cell lines. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 55-61 34767636-4 2021 Interestingly, the residual hypertrophy after Raptor deletion can be completely prevented by administration of the mTORC1 inhibitor rapamycin. Sirolimus 132-141 CREB regulated transcription coactivator 1 Mus musculus 115-121 34309811-6 2021 These phenotypic abnormalities in zebrafish embryos and larvae were rescued by treatment with the mTORC1 inhibitor rapamycin. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 98-104 34672766-3 2021 Regulated in DNA damage and development 1 (REDD1) is a stress-response protein that is transcriptionally upregulated in muscle during wasting conditions and inhibits mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 209-215 34795452-2 2021 Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2-4, but how these environmental signals are integrated for immune regulation remains unclear. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 34916960-5 2021 Surprisingly, aging lends unique atrophy resistance to tibialis anteria muscle, accompanied by an increase in the cascade of mammalian target of rapamycin complex 1 (mTORC1)-independent anabolic events involving Akt signaling, rRNA biogenesis, and protein synthesis during denervation. Sirolimus 145-154 CREB regulated transcription coactivator 1 Mus musculus 166-172 34861413-4 2022 Grb10-deficient beta-cells exhibit enhanced mTORC1 signaling and reduced beta-cell dedifferentiation, which could be blocked by rapamycin. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 44-50 34850372-3 2022 Metformin activates AMP-activated kinase (AMPK), which inhibits mechanistic target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 107-113 34917890-2 2021 The phosphoinositide 3-kinase (PI3K) promotes degradation of PDCD4 via mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 34806651-1 2021 Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 183-189 34520980-5 2021 Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 144-153 CREB regulated transcription coactivator 1 Mus musculus 165-171 34453429-2 2021 Glutamine is used as an energy substrate and is involved in the activation of mechanistic target of rapamycin complex 1 (mTORC1) during porcine preimplantation development. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 121-127 34780278-10 2022 SP-A-induced activation of mechanistic target of rapamycin complex 1 (mTORC1) kinase requires beta-arrestin2 and is critically involved in degradation of LPS-induced TLR4. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 70-76 34562654-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) acts as a central regulator of metabolic pathways that drive cellular growth. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34717796-2 2021 We found that IL-3-induced Janus kinase 2-dependent expression of SLC7A5 and SLC3A2, which comprise the large neutral amino acid transporter, was required for mammalian target of rapamycin complex 1 (mTORC1) nutrient sensor activation in response to toll-like receptor agonists. Sirolimus 179-188 CREB regulated transcription coactivator 1 Mus musculus 200-206 34858182-4 2021 Methods and Results: Immunoblotting analyses revealed that short-term exposure to rapamycin (6h) significantly reduced phosphorylation of p70S6K (mTORC1-specific) in hPASMCs but had no effect on the phosphorylation of AKT (p-AKT S473, considered mTORC2-specific). Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 146-152 34858401-8 2021 Notably, TBK1 inhibition prevented LPS-induced NLRP3 inflammasome activation by targeting the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 135-141 34607910-7 2021 The GTPase RagD encoded by RRAGD plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 130-136 34829625-5 2021 In addition, TET mitigated excessive apoptosis and restored autophagy in the renal cortex, as well as suppressed the development of morphological abnormalities in the mitochondria of proximal tubular cells, which were also accompanied by the restoration of AMP-activated kinase (AMPK) activity and suppression of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 339-348 CREB regulated transcription coactivator 1 Mus musculus 360-366 34233960-7 2021 Subsequent investigations revealed that aberrantly activated mTORC1 signaling in CAR-T cells results in decreased bone marrow infiltration and decreased the levels of the rapamycin target CXCR4. Sirolimus 171-180 CREB regulated transcription coactivator 1 Mus musculus 61-67 34233960-8 2021 Attenuating mTORC1 activity with the rapamycin pretreatment increased the capacity of CAR-T cells to infiltrate bone marrow and enhanced the extent of bone marrow AML cell elimination in leukemia xenograft mouse models. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 12-18 34398293-4 2021 Initiation of autophagy is regulated by two key components of the nutrient/energy sensor pathways; mammalian target of rapamycin 1 (mTORC1) and AMP-activated kinase (AMPK). Sirolimus 119-128 CREB regulated transcription coactivator 1 Mus musculus 132-138 34364639-9 2021 Also, IGF-1-induced XBP1s and ER biogenesis-associated gene expression was inhibited by rapamycin, an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), indicating that IRE1-XBP1 activation by IGF-1 is mediated by mTORC1. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 115-121 34561230-5 2021 IFN-gamma stimulation conferred on M0 macrophages the sensitivity to SM-induced cell death through the Jak/STAT, IFN regulatory factor-1, and mammalian target of rapamycin complex-1 (mTORC-1)/ribosomal protein S6 kinase pathways. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 183-190 34478760-1 2021 AIMS: The sustained activation of intestinal mechanistic target of rapamycin complex 1 (mTORC1) brought about by repeated mucosal insult or injury has been linked to escalation of gut inflammatory response, which may progress to damage the epithelium if not controlled. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 88-94 34733478-3 2021 Recent findings support the impairment of the mammalian target of rapamycin complex 1 (mTORC1) in MDD. Sirolimus 66-75 CREB regulated transcription coactivator 1 Mus musculus 87-93 34341503-2 2021 Previous work has shown that the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1) is involved in generating protective ILC3 cytokine responses during bacterial infection. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 98-104 34757123-6 2022 The mTOR inhibitor, rapamycin, completely abolished activation of mTORC1 and mTORC2 after long term treatment with receptor antibodies. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 66-72 34853810-1 2021 Loss of function of tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) leads to the activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 116-125 CREB regulated transcription coactivator 1 Mus musculus 137-143 34303878-1 2021 OBJECTIVE: The mechanistic target of rapamycin complex 1 (mTORC1) is dynamically regulated by fasting and feeding cycles in the liver to promote protein and lipid synthesis while suppressing autophagy. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 34303878-4 2021 METHODS: ATF4 protein levels and expression of canonical gene targets were analyzed in the liver following fasting and physiological feeding in the presence or absence of the mTORC1 inhibitor rapamycin. Sirolimus 192-201 CREB regulated transcription coactivator 1 Mus musculus 175-181 34778262-2 2021 In response to nutrient shortage and stresses, the TSC complex inhibits the mechanistic target of rapamycin complex 1 (mTORC1) at the lysosomes. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 119-125 34482023-1 2021 Ras-related GTP binding (Rag) GTPases are required to activate mechanistic target of rapamycin complex 1 (mTORC1), which plays a central role in cell growth and metabolism and is considered as one of the most important oncogenic pathways. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 106-112 34677125-3 2021 Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Muller glia (MG) that degenerate from senescence-associated cell death. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 85-91 34685691-5 2021 Moreover, analysis of SZT2 ablated cells revealed increased mTORC1 signaling activation that could be reversed by Rapamycin or Torin treatments. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 60-66 34673774-1 2021 The mammalian target of rapamycin complex 1 (mTORC1) senses multiple stimuli to regulate anabolic and catabolic processes. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 34644574-3 2021 Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 135-141 34633285-2 2021 Paneth cells rely heavily on the glycolytic metabolic program, which is in part controlled by the kinase complex Mechanistic target of rapamycin (mTORC1). Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 146-152 34459485-4 2021 Cultured mouse-C2C12 skeletal muscle cells were treated with mammalian target of rapamycin complex 1 (mTORC1) or protein kinase b (Akt) inhibitor, and protein synthesis was quantified. Sirolimus 81-90 CREB regulated transcription coactivator 1 Mus musculus 102-108 34735882-1 2021 Abnormal activation of the mechanistic target of rapamycin (mTOR) signaling is commonly observed in many cancers and attracts extensive attention as an oncology drug discovery target, which is encouraged by the success of rapamycin and its analogs (rapalogs) in treatment of mTORC1-hyperactive cancers in both pre-clinic models and clinical trials. Sirolimus 222-231 CREB regulated transcription coactivator 1 Mus musculus 275-281 34735882-5 2021 Mechanistically, we found that hayatine disrupts the interaction between mTORC1 complex and its lysosomal adaptor RagA/C by binding to the hydrophobic loop of RagC, leading to mTORC1 inhibition that holds great promise to overcome rapamycin resistance. Sirolimus 231-240 CREB regulated transcription coactivator 1 Mus musculus 73-79 34685712-2 2021 The present study aimed to investigate if mechanistic target of rapamycin complex 1 (mTORC1) plays a role in FFA-induced organelle dysfunction, thereby contributing to the development of ALD. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 85-91 34685712-4 2021 C57BL/6J wild-type mice were subjected to chronic alcohol feeding with or without rapamycin to inhibit mTORC1 activation. Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 103-109 34685712-5 2021 We revealed that palmitic acid (PA)-induced ER stress and suppression of LAMP2 and autophagy flux were mTORC1-dependent as rapamycin reversed such deleterious effects. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 103-109 34685712-7 2021 Supplementation with rapamycin to alcohol-fed mice attenuated mTORC1 activation and ER stress, restored LAMP2 protein, and improved autophagy, leading to amelioration of alcohol-induced liver injury. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 62-68 34097069-1 2021 OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioural therapy(CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of mRNA expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. Sirolimus 354-363 CREB regulated transcription coactivator 1 Mus musculus 367-373 34620223-7 2021 Rap and Rap+Met inhibited articular cartilage mTORC1 but not mTORC2 signaling. Sirolimus 0-3 CREB regulated transcription coactivator 1 Mus musculus 46-52 34620223-7 2021 Rap and Rap+Met inhibited articular cartilage mTORC1 but not mTORC2 signaling. Sirolimus 8-12 CREB regulated transcription coactivator 1 Mus musculus 46-52 34636300-5 2022 The mechanistic target of rapamycin complex1 (mTORC1) is a promising candidate. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 46-52 34636300-8 2022

Methods: The perspective grounds its method on recent literature along with the actual experimental procedure to elicit status epilepticus from the piriform cortex and the method to administer the mTORC1 inhibitor rapamycin to mitigate seizure expression and brain damage. Sirolimus 218-227 CREB regulated transcription coactivator 1 Mus musculus 201-207 34544857-1 2021 Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either TSC1 or TSC2 Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking up-regulation of Interleukin-6 (IL-6). Sirolimus 113-122 CREB regulated transcription coactivator 1 Mus musculus 134-140 34461118-4 2021 In contrast to simvastatin, the mTORC1 inhibitor rapamycin did not inhibit mTORC2 activity and was not cytotoxic. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 32-38 34523696-4 2021 Rapamycin and its analogs were less successful in clinical trials for patients with GB due to their incomplete inhibition of mTORC1 and the activation of mitogenic pathways via negative feedback loops. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 125-131 34546793-0 2021 Dissecting the biology of mTORC1 beyond rapamycin. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 26-32 34325132-2 2021 In response to nutrient cue, tuberous sclerosis complex (TSC) works as a tumor suppressor which inhibits cell growth via negative regulation of the mammalian target of rapamycin complex (mTORC1). Sirolimus 168-177 CREB regulated transcription coactivator 1 Mus musculus 187-193 34518220-8 2021 mTORC1 inhibition with rapamycin analog Ridaforolimus suppresses TRIM28 phosphorylation, hTERT expression, and cell viability. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 0-6 34519641-5 2021 Moreover, we demonstrate that these pathways are involved in the demyelination process, and that inhibition of mTORC1 using rapamycin partially rescues the demyelinating pathology. Sirolimus 124-133 CREB regulated transcription coactivator 1 Mus musculus 111-117 34246831-1 2021 Amino acids can affect protein synthesis by activating mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 96-102 34589488-4 2021 Studies in this model have identified that decanoic acid reduces phosphoinositide turnover, diacylglycerol kinase (DGK) activity, and also inhibits the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 174-183 CREB regulated transcription coactivator 1 Mus musculus 195-201 34589493-2 2021 Previous studies have shown that Rg3 treatment downregulates the activity of rapamycin complex 1 (mTORC1) activity and inhibits the growth of cancer cells. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 98-104 34388363-3 2021 Sestrins are a class of stress-inducible proteins that act as antioxidants and inhibit the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling complex. Sirolimus 129-138 CREB regulated transcription coactivator 1 Mus musculus 150-156 34243067-1 2021 The mammalian target of rapamycin complex 1 (mTORC1) is a crucial regulator of adipogenesis and systemic energy metabolism. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 34646153-5 2021 This prioritization/interference may be due to the interplay between the 5" AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) signaling cascades and/or the high skeletal muscle energy requirements for the synthesis and maintenance of cellular organelles. Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 159-165 34575924-6 2021 Here, we introduce the current knowledge of hypoxia signaling with two-well known cellular energy and nutrient sensing pathways, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 191-200 CREB regulated transcription coactivator 1 Mus musculus 212-218 34378991-5 2021 Here, we demonstrated that palmitate upregulates NNMT expression via activating ATF4 in a mechanistic target of rapamycin complex 1 (mTORC1)-dependent mechanism in that mTORC1 inhibition by both Torin1 and rapamycin attenuated ATF4 activation and NNMT upregulation. Sirolimus 206-215 CREB regulated transcription coactivator 1 Mus musculus 133-139 34572527-1 2021 Amino acids are critical for mammalian target of rapamycin complex 1 (mTORC1) activation on the lysosomal surface. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 70-76 34378991-5 2021 Here, we demonstrated that palmitate upregulates NNMT expression via activating ATF4 in a mechanistic target of rapamycin complex 1 (mTORC1)-dependent mechanism in that mTORC1 inhibition by both Torin1 and rapamycin attenuated ATF4 activation and NNMT upregulation. Sirolimus 112-121 CREB regulated transcription coactivator 1 Mus musculus 133-139 34378991-5 2021 Here, we demonstrated that palmitate upregulates NNMT expression via activating ATF4 in a mechanistic target of rapamycin complex 1 (mTORC1)-dependent mechanism in that mTORC1 inhibition by both Torin1 and rapamycin attenuated ATF4 activation and NNMT upregulation. Sirolimus 206-215 CREB regulated transcription coactivator 1 Mus musculus 169-175 34187836-1 2021 Transmembrane 4 L six family member 5 (TM4SF5) functions as a sensor for lysosomal arginine levels and activates the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 137-146 CREB regulated transcription coactivator 1 Mus musculus 158-164 34081952-1 2021 RATIONALE: The nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) and its primary inhibitor, tuberin (TSC2), are cues for the development of cardiac hypertrophy. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 75-81 34280391-4 2021 GS catalyzes the transformation of neurotoxic glutamate (Glu) into nontoxic glutamine (Gln) to activate the mammalian target of rapamycin complex 1 (mTORC1), which promotes the activation of RMCs. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 149-155 34294367-3 2021 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 195-204 CREB regulated transcription coactivator 1 Mus musculus 216-222 34294370-3 2021 Preclinical studies have revealed that the antidepressant actions of ketamine are mediated via the release of brain-derived neurotrophic factor and vascular endothelial growth factor, with the subsequent activation of mechanistic target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex. Sirolimus 240-249 CREB regulated transcription coactivator 1 Mus musculus 261-267 34429398-8 2021 Once induced, SESN2 halted protein synthesis by inhibiting the mammalian target of rapamycin complex 1 (mTORC1), thereby attenuating ERS. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 104-110 34503187-2 2021 Intracellular levels of free amino acids, especially leucine, regulate the mammalian target of rapamycin complex 1 (mTORC1) activation. Sirolimus 95-104 CREB regulated transcription coactivator 1 Mus musculus 116-122 34703880-6 2021 Mechanistically, OA selectively targeted superoxide dismutase 1 (SOD1) and yielded reactive oxygen species (ROS) to activate the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/macroautophagy pathway, thus eliciting lysosomal degradation of HGPRT and 5"-NT. Sirolimus 185-194 CREB regulated transcription coactivator 1 Mus musculus 206-212 34175438-1 2021 Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and activated mTORC1 plays important roles for cellular survival in response to oxidative stress. Sirolimus 74-83 CREB regulated transcription coactivator 1 Mus musculus 95-101 34175438-1 2021 Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and activated mTORC1 plays important roles for cellular survival in response to oxidative stress. Sirolimus 74-83 CREB regulated transcription coactivator 1 Mus musculus 117-123 34245671-5 2021 Here, we show that the mechanistic target of rapamycin complex 1 (mTORC1) directly phosphorylates GRASP55 to maintain its Golgi localization, thus revealing a physiological role for mTORC1 at this organelle. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 66-72 34245671-5 2021 Here, we show that the mechanistic target of rapamycin complex 1 (mTORC1) directly phosphorylates GRASP55 to maintain its Golgi localization, thus revealing a physiological role for mTORC1 at this organelle. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 182-188 34348155-4 2021 Sustained hyper-activation of mechanistic target of rapamycin complex 1 (mTORC1) is the primary mechanism of the PHLPP upregulation linking chronic metabolic stress to ultimate beta-cell death. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 73-79 34385317-2 2021 Toll-like receptor (TLR)7/9- and nucleotide-binding oligomerization domain-containing protein 1 (NOD1)-mediated inflammatory responses require SLC15A4 function for regulating the mechanistic target of rapamycin complex 1 (mTORC1) or transporting L-Ala-gamma-D-Glu-meso-diaminopimelic acid, IL-12: interleukin-12 (Tri-DAP), respectively. Sirolimus 201-210 CREB regulated transcription coactivator 1 Mus musculus 222-228 34445471-1 2021 The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, Ras homolog enriched in brain (RHEB-GTPase). Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 57-63 34389720-4 2021 LATS2 activates mechanistic target of rapamycin complex 1 (mTORC1), a physiological suppressor of autophagy, in beta-cells and genetic and pharmacological inhibition of mTORC1 counteracts the pro-apoptotic action of activated LATS2. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 59-65 34343111-9 2021 And the mTORC1 inhibitor, Rapamycin, has been proved to exert neuroprotective effects in the ultra-early and early cerebral ischemia-reperfusion. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 8-14 34341336-5 2021 PLA enhanced FGFBP1 expression through activation of the mechanistic target of rapamycin complex 1-signal transducer and activator of transcription 3 (mTORC1-STAT3) signaling pathway. Sirolimus 79-88 CREB regulated transcription coactivator 1 Mus musculus 151-157 34512126-6 2021 In the intestinal epithelium, CR suppresses the mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells to shift the stem cell equilibrium towards self-renewal at the cost of differentiation. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 91-97 34189960-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) signaling complex is emerging as a critical regulator of cardiovascular function with alterations in this pathway implicated in cardiovascular diseases. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34121197-4 2021 Other regulators of ferroptosis have also been discovered recently, among them the mechanistic target of rapamycin complex 1 (mTORC1), a central controller of cell growth and metabolism. Sirolimus 105-114 CREB regulated transcription coactivator 1 Mus musculus 126-132 34326413-4 2021 Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 61-67 34301883-1 2021 Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor that functions together with Tsc2 to negatively regulate the mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 141-150 CREB regulated transcription coactivator 1 Mus musculus 162-168 34393724-4 2021 Most importantly, AMPK activation is known to suppress the translational machinery by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), activating translational regulators, and phosphorylating nuclear transporter factors. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 144-150 34440627-7 2021 The mutation in Eif2b5 prompts reactive oxygen species (ROS)-mediated inferior ability to stimulate the AMP-activated protein kinase (AMPK) axis, due to a requirement to increase the mammalian target of rapamycin complex-1 (mTORC1) signalling in order to enable oxidative glycolysis and generation of specific subclass of ROS-regulating proteins, similar to cancer cells. Sirolimus 203-212 CREB regulated transcription coactivator 1 Mus musculus 224-230 34244482-4 2021 Here we report that mechanistic target of rapamycin complex 1 (mTORC1) signal inhibits GLDC acetylation at lysine (K) 514 by inducing transcription of the deacetylase sirtuin 3 (SIRT3). Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 63-69 34349839-1 2021 Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that antagonise the mammalian isoform of the target of rapamycin complex 1 (mTORC1) - a key mediator of cell growth and metabolism. Sirolimus 184-193 CREB regulated transcription coactivator 1 Mus musculus 205-211 34267188-2 2021 DEP domain-containing protein 5 (DEPDC5), a component of GAP activities towards Rags 1 (GATOR1) complex, is a repressor of amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 176-185 CREB regulated transcription coactivator 1 Mus musculus 197-203 34354601-2 2021 They also serve as signaling molecules, for example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 129-135 34354602-11 2021 Rapalink-1 significantly decreased phosphorylated S6 and Akt to half the level of the control rats in the IR-C, which suggests that both of the mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2) were inhibited. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 193-199 34336098-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) signaling plays pivotal roles in cell growth and diseases. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34253722-1 2021 Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 149-155 34233775-5 2021 In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Sirolimus 149-158 CREB regulated transcription coactivator 1 Mus musculus 170-176 34209274-4 2021 The mammalian target of the Rapamycin (mTOR) signaling pathway that acts via two distinct multiprotein complexes, mTORC1 and mTORC2, can affect oxidative stress. Sirolimus 28-37 CREB regulated transcription coactivator 1 Mus musculus 114-120 34143450-4 2021 The mammalian target of rapamycin complex 1 (mTORC1) signaling on late endosomes (LEs)/lysosomes may control cargo selection, membrane biogenesis, and exosome secretion, which may be fine controlled by lysosomal sphingolipids such as CER. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 34087234-8 2021 Phosphorylation of p62 at Ser349 by mammalian target of rapamycin complex 1 (mTORC1), a critical step in p62-Keap1 interaction, was induced by I/R, but diminished by R1alpha loss. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 77-83 34116056-1 2021 Cellular growth and proliferation are primarily dictated by the mechanistic target of rapamycin complex 1 (mTORC1), which balances nutrient availability against the cell"s anabolic needs. Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 107-113 34075648-2 2021 In cancer cells, glutamine has been implicated in the activation of mechanistic target of rapamycin complex 1 (mTORC1) to support rapid proliferation. Sirolimus 90-99 CREB regulated transcription coactivator 1 Mus musculus 111-117 34258253-3 2021 Here, we propose a plausible molecular mechanism, wherein cryptotanshinone represses rapamycin-sensitive mTORC1/S6K1 mediated cancer cell growth and cell transformation. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 105-111 34187514-6 2021 We show that the harmful effect of AMPK is exerted through inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 118-124 34209274-6 2021 Thus, Rapamycin-a selective inhibitor of mTORC1, Torin-2-a non-selective mTORC1/mTORC2 inhibitor, and FK-506-a drug that impacts oxidative stress in an mTOR-independent manner were used. Sirolimus 6-15 CREB regulated transcription coactivator 1 Mus musculus 41-47 34209274-12 2021 Because these effects were completely reversed by Rapamycin, an mTORC1 inhibitor, this outcome suggests its usefulness as a preventive therapy in disorders connected with prenatal ethanol exposure. Sirolimus 50-59 CREB regulated transcription coactivator 1 Mus musculus 64-70 34099704-1 2021 Lysosomes are involved in nutrient sensing via the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 94-100 34135321-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) integrates cellular nutrient signaling and hormonal cues to control metabolism. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34135323-1 2021 The Mechanistic Target Of Rapamycin Complex 1 (mTORC1) pathway controls several aspects of neuronal development. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34198993-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) is a master growth regulator by controlling protein synthesis and autophagy in response to environmental cues. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 34234741-3 2021 The YO transitions through four physiological states over the molt cycle, which are mediated by molt-inhibiting hormone (MIH; basal state), mechanistic Target of Rapamycin Complex 1 (mTORC1; activated state), Transforming Growth Factor-beta (TGFbeta)/Activin (committed state), and ecdysteroid (repressed state) signaling pathways. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 183-189 34073791-2 2021 Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 112-118 34195689-1 2021 Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) is a major signalling kinase in cells that regulates proliferation and metabolism and is controlled by extrinsic and intrinsic signals. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 34073791-2 2021 Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. Sirolimus 79-83 CREB regulated transcription coactivator 1 Mus musculus 112-118 35439535-7 2022 Our results also confirmed that mTOR inhibitor sensitized senolytic cell death is apoptotic and pan-mTOR inhibitors PP242 and AZD8055 works more effectively than mTORC1 inhibitor Rapamycin. Sirolimus 179-188 CREB regulated transcription coactivator 1 Mus musculus 162-168 35460832-6 2022 Rapamycin-induced blockage of mTOR complex 1 (mTORC1) signaling, which regulates metabolism, differentially inhibited LF- and HF-modulated protein signatures of mitochondrial NADH dehydrogenase ubiquinone flavoprotein 2, mitochondrial glutathione peroxidase 4, kynureninase, and alpha-crystallin B chain as well as programmed cell death 5 in transcript levels; it subsequently diminished apoptosis and oncospheroid formation in LF/HF-exposed cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 46-52 35486977-5 2022 From the additional compounds that could reverse this metabolic reprogramming, the mTORC1 inhibitor sirolimus was selected. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 83-89 35107743-11 2022 Rapamycin is the most famous inhibitor of mTORC1 among all. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 42-48 35291809-4 2022 Since initial studies found that the acute increase of RPP resulted in activation of mTORC1 (phosphorylation of S6S235/236), the effects of inhibition of mTORC1 with rapamycin pretreatment were then determined. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 154-160 35597502-2 2022 Sestrin2 content is involved in the function of mechanistic target of rapamycin complex 1 (mTORC1) in mouse embryonic fibroblasts and C2C12 cells. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 91-97 35488725-4 2022 The mTOR inhibitor sirolimus, which preferentially inhibits mTORC1, has led to sustained remission in a small cohort of anti-IL-6-refractory iMCD patients with thrombocytopenia, anasarca, fever, renal dysfunction and organomegaly (iMCD-TAFRO). Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 60-66 35623884-3 2022 Targeting the key metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) and its downstream pathway shows efficacy only in subsets of patients but gene modifiers maximising response remain to be identified. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 81-87 35589683-3 2022 p53 inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling to attenuate the protein level of mitochondrial fission process 1 (MTFP1), which fosters the pro-fission dynamin-related protein 1 (Drp1) phosphorylation. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 35585420-2 2022 The synthesis, uptake, and efflux of cellular cholesterol are significantly linked to the mammalian target of rapamycin complex-1 (mTORC1). Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 131-137 35442666-3 2022 The cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1) is a crucial upstream regulator of the mechanistic target of rapamycin complex 1 (mTORC1) signaling, which has close connections with apoptosis. Sirolimus 122-131 CREB regulated transcription coactivator 1 Mus musculus 34-40 35561222-1 2022 SignificanceThe mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is frequently elevated in human disease, including cancer, type 2 diabetes, metabolic disorders, and neurodegeneration. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 57-63 35561748-1 2022 Mechanistic target of rapamycin complex 1 (mTORC1) is a multi-protein complex widely found in eukaryotes. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 35560184-5 2022 Furthermore, IGF1Rhi Tregs exhibited higher phosphorylation of the mammalian target of the rapamycin complex 1 (mTORC1) in vivo. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 35577075-1 2022 The mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase complex that promotes anabolic processes including protein, lipid, and nucleotide synthesis, while suppressing catabolic processes such as macroautophagy. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 35538662-6 2022 Specific inhibition of mTORC1 using rapamycin also induced changes in the expression of metabolic genes. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 23-29 35527284-6 2022 Furthermore, Sestrin2 can vigorously inhibit oncogenic signaling pathways through downregulation of mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor 1-alpha (HIF-1alpha). Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 141-147 35563840-7 2022 The loss of Lcn2 dismisses the effect of mTORC1 inhibition by rapamycin on COX2, thermogenesis genes, lipogenesis, and lipolysis, but has no impact on p70 S6Kinase-ULK1 activation in Lcn2-deficient adipocytes. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 41-47 35442666-3 2022 The cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1) is a crucial upstream regulator of the mechanistic target of rapamycin complex 1 (mTORC1) signaling, which has close connections with apoptosis. Sirolimus 122-131 CREB regulated transcription coactivator 1 Mus musculus 143-149 35441596-6 2022 In addition, HRI-elF2alphaP specifically enhances translation of ATF4 mRNA leading to the repression of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 147-153 35437883-8 2022 Further investigation uncovered that H19 also acted as an orchestra conductor that inhibited the function of mechanistic target of rapamycin complex 1 (mTORC1) by disrupting the interaction of mTORC1 with eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1). Sirolimus 131-140 CREB regulated transcription coactivator 1 Mus musculus 152-158 34435708-3 2022 Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 35437883-8 2022 Further investigation uncovered that H19 also acted as an orchestra conductor that inhibited the function of mechanistic target of rapamycin complex 1 (mTORC1) by disrupting the interaction of mTORC1 with eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1). Sirolimus 131-140 CREB regulated transcription coactivator 1 Mus musculus 193-199 35573741-1 2022 Objective: The mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway has emerged as a crucial player in the oncogenesis and development of head and neck squamous cell carcinoma (HNSCC), however, to date, no relevant gene signature has been identified. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 60-66 35293604-3 2022 Here, we define the role of intracellular zinc in axon formation and elongation, involving the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 136-142 35503070-9 2022 The expression levels of Beclin-1, microtubule- associated protein light chain 3-II (LC3-II), mammalian target of rapamycin complex 1 (mTORC1), and VEGF were measured by immunohistochemistry and Western blot. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 135-141 35547814-9 2022 Rapamycin significantly blocked mTORC1 signaling pathway in the irradiated testis. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 32-38 35547814-10 2022 Inhibition of mTORC1 signaling pathway by rapamycin treatment after radiation could significantly improve cell proliferation in testis and alleviate radiation-induced testicular injury after radiation exposure. Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 14-20 35547814-12 2022 These findings imply that rapamycin treatment can accelerate testis recovery under radiation condition through inhibiting mTORC1 signaling pathway. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 122-128 35547764-6 2022 Methods: We profiled mTORC1-dependent long non-coding RNAs (lncRNAs) by RNA-seq of HCC cells treated with rapamycin. Sirolimus 106-115 CREB regulated transcription coactivator 1 Mus musculus 21-27 35461323-8 2022 Electron microscopy analysis revealed that the number of lysosomes increased relative to that of MVBs and the level of EVs decreased after treatment with asteltoxin or rapamycin, an mTORC1 inhibitor. Sirolimus 168-177 CREB regulated transcription coactivator 1 Mus musculus 182-188 35436937-9 2022 Correspondingly, the expressions of Nrf2, Atm, Atr, and Prkdc in IVM oocytes were markedly increased, following the inhibition of mTORC1 pathway by 10 nM rapamycin. Sirolimus 154-163 CREB regulated transcription coactivator 1 Mus musculus 130-136 35440545-4 2022 The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 4-10 35436937-11 2022 The inhibition of mTORC1 pathway, which involved in activating DDR-associated genes may act as a potential mechanism for oocyte quality improvement by rapamycin. Sirolimus 151-160 CREB regulated transcription coactivator 1 Mus musculus 18-24 35219732-4 2022 A detailed description of signaling pathways of mTORC1 and mTORC2 that are inhibited by rapamycin and other mTOR inhibitor analogues is accentuated. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 48-54 35101523-3 2022 The parent study for the secondary pilot analyses presented here was a double-blind, cross-over trial that found pretreatment with the mechanistic target of rapamycin complex 1 (mTORC1) prolonged the antidepressant effects of ketamine. Sirolimus 157-166 CREB regulated transcription coactivator 1 Mus musculus 178-184 35420934-2 2022 The mechanistic target of rapamycin complex 1 (mTORC1) pathway is a potential therapeutic target, but conflicting interpretations have been proposed for how mTORC1 controls lipid homeostasis. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 35420934-2 2022 The mechanistic target of rapamycin complex 1 (mTORC1) pathway is a potential therapeutic target, but conflicting interpretations have been proposed for how mTORC1 controls lipid homeostasis. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 157-163 35321785-3 2022 Under nutrient-rich conditions, mTOR complex 1 (mTORC1) phosphorylates the ULK1 complex, preventing its activation and subsequent autophagosome formation, while inhibition of mTORC1 using either rapamycin or nutrient deprivation induces autophagy. Sirolimus 195-204 CREB regulated transcription coactivator 1 Mus musculus 175-181 35457142-4 2022 BCAAs-in particular leucine-activate the rapamycin complex1 mTORC1, which regulates cell growth and metabolism, glucose metabolism and several more essential physiological processes. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 60-66 35444643-7 2022 The combined effects of IL-4 and SP-A on the mTORC1 and GSK3 branches of PI3K-Akt signaling contribute to increased AM proliferation and alternative activation, as revealed by pharmacological inhibition of Akt (inhibitor VIII) and mTORC1 (rapamycin and torin). Sirolimus 239-248 CREB regulated transcription coactivator 1 Mus musculus 45-51 35379807-1 2022 Activation of the cannabinoid-1 receptor (CB1R) and the mammalian target of rapamycin complex 1 (mTORC1) in the renal proximal tubular cells (RPTCs) contributes to the development of diabetic kidney disease (DKD). Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 97-103 35321881-6 2022 The MAPK and mammalian target of rapamycin complex 1 (mTORC1) axes, which are involved in TCR-mediated signaling, were also required for LcIL-2-mediated T cell response. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 54-60 35433951-11 2022 JPTGY affects browning of 3T3-L1 cells through mechanistic target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 90-96 35368869-4 2022 While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Sirolimus 208-217 CREB regulated transcription coactivator 1 Mus musculus 229-235 35318320-3 2022 Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. Sirolimus 134-143 CREB regulated transcription coactivator 1 Mus musculus 155-161 35275792-4 2022 This study suggests that chronic activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway in degenerating photoreceptor neurons could stimulate the degradation of ubiquitinated proteins and enhance proteasomal activity through phosphorylation. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 92-98 35165201-2 2022 NPRL2 is a requisite subunit of the Gap Activity TOward Rags 1 (GATOR1) complex, which functions as a negative regulator of mammalian Target Of Rapamycin Complex 1 (mTORC1) kinase when intracellular amino acids are low. Sirolimus 144-153 CREB regulated transcription coactivator 1 Mus musculus 165-171 35358174-1 2022 Mechanistic target of rapamycin complex I (mTORC1) is central to cellular metabolic regulation. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 35401560-6 2022 T-cell receptor (TCR), mechanistic target of rapamycin complex 1 (mTORC1), myelocytomatosis oncogene (MYC) signaling pathways and E2F6 might be "master regulators" of glycolytic activity. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 66-72 35359988-6 2022 Mechanistically, we discovered that the mammalian target of rapamycin complex 1 (mTORC1) signaling inhibition leads to decreased glycolysis and OXPHOS in dNK. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 81-87 35238644-3 2022 We previously demonstrated the efficacy of sirolimus in ARHL in mice by decreasing mTORC1. Sirolimus 43-52 CREB regulated transcription coactivator 1 Mus musculus 83-89 35165201-7 2022 Targeted deletion of NPRL2 in primary neurons increases the expression of sodium channel Scn1A, whereas treatment with the pharmacological mTORC1 inhibitor called rapamycin prevents Scn1A upregulation. Sirolimus 163-172 CREB regulated transcription coactivator 1 Mus musculus 139-145 35235777-6 2022 Rather, loss of Slc6a8 or Ckb disrupts naive T cell homeostasis and weakens TCR-mediated activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling required for CD8+ T cell expansion. Sirolimus 125-134 CREB regulated transcription coactivator 1 Mus musculus 146-152 35020443-2 2022 The nuclear localization of TFEB is blocked by the mechanistic target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of TFEB at multiple sites including Ser-211. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 94-100 35183507-1 2022 The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is activated by intracellular nutritional sufficiency and extracellular growth signals. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 35171658-1 2022 PURPOSE: Sapanisertib is a kinase inhibitor that inhibits both mammalian target of rapamycin complex 1 (mTORC1) and mTORC2. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 104-110 35196486-5 2022 Molecular analyses reveal that loss of Slc38a4 imprinting leads to over-activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway in cloned placentae, which is likely due to the increased amino acids transport by SLC38A4. Sirolimus 112-121 CREB regulated transcription coactivator 1 Mus musculus 133-139 35172150-1 2022 AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are metabolic kinases that co-ordinate nutrient supply with cell growth. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 83-89 35044284-6 2022 Mechanistically, we found elevated phosphorylation of AKT and two downstream effectors of mammalian target of Rapamycin complex 1 (mTORC1), S6 and 4E-Binding Protein 1 (4EBP1) after Rasal2 overexpression in hypoxia-challenged PASMC. Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 131-137 35163619-1 2022 Classically activated M1 macrophages reprogram their metabolism towards enhanced glycolysis to obtain energy and produce pro-inflammatory cytokines after activation by mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor (HIF)-1alpha. Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 209-215 35181635-1 2022 Lymphangioleiomyomatosis (LAM) is a rare progressive disease, characterized by mutations in the tuberous sclerosis complex genes (TSC1 or TSC2) and hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 189-198 CREB regulated transcription coactivator 1 Mus musculus 210-216 35136019-2 2022 Vertebrate retinal development involves a delicate and coordinated process of retinal progenitor cell (RPC) differentiation, and the mammalian target of rapamycin complex 1 (mTORC1) has been reported to play a significant role in this complex process. Sirolimus 153-162 CREB regulated transcription coactivator 1 Mus musculus 174-180 35134872-10 2022 Further studies showed that L-arginine, a GPRC6A agonist, promoted colonic ILC3 expansion and function via mammalian target of rapamycin complex 1 (mTORC1) signalling in vitro. Sirolimus 127-136 CREB regulated transcription coactivator 1 Mus musculus 148-154 35153674-3 2021 In this study, we found that hearing loss and OM infections in OM mice were significantly alleviated after treatment with rapamycin (RPM), a widely used mechanistic target of RPM complex 1 (mTORC1) inhibitor and autophagy inducer. Sirolimus 122-131 CREB regulated transcription coactivator 1 Mus musculus 190-196 35153674-3 2021 In this study, we found that hearing loss and OM infections in OM mice were significantly alleviated after treatment with rapamycin (RPM), a widely used mechanistic target of RPM complex 1 (mTORC1) inhibitor and autophagy inducer. Sirolimus 133-136 CREB regulated transcription coactivator 1 Mus musculus 190-196 35128865-1 2022 OBJECTIVE: To investigate the effects of electroacupuncture (EA) on the expression of related proteins in the brain-derived neurotrophic factor (BDNF)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and synapse-associated proteins and the density of dendrite spines in the prefrontal cortex (PFC) of depression model rats, and to reveal the underlying mechanism by which EA regulates the synaptic plasticity to improve depressive symptoms. Sirolimus 171-180 CREB regulated transcription coactivator 1 Mus musculus 192-198 35125916-3 2022 The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of protein metabolism in cells. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 35022234-2 2022 Amino acid and growth factor signaling pathways coordinately regulate the mechanistic target of rapamycin complex 1 (mTORC1) kinase in cell growth and organ development. Sirolimus 96-105 CREB regulated transcription coactivator 1 Mus musculus 117-123 35114453-9 2022 Mechanistically, ISL activates adenosine monophosphate-activated protein kinase (AMPK) and inhibits mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 141-147 34979914-2 2022 Sesns regulate metabolism mainly through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 151-160 CREB regulated transcription coactivator 1 Mus musculus 172-178 35240344-3 2022 Downstream of insulin signaling, the mechanistic target of rapamycin complex 1 (mTORC1), is a key regulator of lipid metabolism. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 80-86 33756106-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient, growth, and oncogenic signals. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 34004356-1 2021 The nutrient sensors peroxisome proliferator-activated receptor gamma (PPARgamma) and mechanistic target of rapamycin complex 1 (mTORC1) closely interact in the regulation of adipocyte lipid storage. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 129-135 33269476-2 2021 Although the critical effect of mechanistic target of rapamycin complex 1 (mTORC1) in shaping mTEC differentiation has been studied, the regulatory role of mTORC2 in the differentiation and maturation of mTECs is poorly understood. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 75-81 35005610-4 2022 Hypoxia also represses all early signaling responses associated with YM155, including activation of AMPK and retinoblastoma protein (Rb), inactivation of the mechanistic target of rapamycin complex 1 (mTORC1), inhibition of phospho-ribosomal protein S6 (rS6), and suppression of the expression of Cyclin Ds, Mcl-1 and Survivin. Sirolimus 180-189 CREB regulated transcription coactivator 1 Mus musculus 201-207 33054526-5 2021 We further confirmed that the translational efficiency of Tudor-SN mRNA was controlled by the mammalian target of rapamycin complex 1 (mTORC1) pathway, as revealed via inhibition of activated mTORC1 in primary neonatal mouse cardiomyocytes and activation of silenced mTORC1 in adult mouse myocardia; additionally, this result was recapitulated in H9c2 cells. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 135-141 34045438-5 2021 mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. Sirolimus 18-27 CREB regulated transcription coactivator 1 Mus musculus 0-6 33949851-12 2021 Similarly, our work developing biosensors to monitor the subcellular mechanistic target of rapamycin complex 1 (mTORC1) signaling allowed us to not only clarify the presence of mTORC1 activity in the nucleus but also identify a novel mechanism governing the activation of mTORC1 in this location. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 33949851-12 2021 Similarly, our work developing biosensors to monitor the subcellular mechanistic target of rapamycin complex 1 (mTORC1) signaling allowed us to not only clarify the presence of mTORC1 activity in the nucleus but also identify a novel mechanism governing the activation of mTORC1 in this location. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 177-183 33949851-12 2021 Similarly, our work developing biosensors to monitor the subcellular mechanistic target of rapamycin complex 1 (mTORC1) signaling allowed us to not only clarify the presence of mTORC1 activity in the nucleus but also identify a novel mechanism governing the activation of mTORC1 in this location. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 177-183 34001117-4 2021 RESULTS: In response to con-specific pheromones indicative of stress, AMP-activated protein kinase (AMPK), mechanistic target of rapamycin complex 1 (mTORC1), and insulin signaling regulate stress resistance and sex determination across one generation, and these effects can be mimicked by pathway modulators. Sirolimus 129-138 CREB regulated transcription coactivator 1 Mus musculus 150-156 34003330-7 2021 Mechanistically, LKB1 directly binds and phosphorylates phosphatase and tensin homolog (PTEN), an upstream regulator of mammalian target of rapamycin complex 1 (mTORC1), which is independent of AMP-activated protein kinase (AMPK). Sirolimus 140-149 CREB regulated transcription coactivator 1 Mus musculus 161-167 33992580-7 2021 Mechanistically, overexpression of ZNRF2 inhibited the over-induction of autophagy induced by OGD/R which was abolished by mTORC1 inhibitor rapamycin. Sirolimus 140-149 CREB regulated transcription coactivator 1 Mus musculus 123-129 33988249-1 2021 The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 33988501-3 2021 Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally, through eIF3-mediated translation. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 32-38 33988501-7 2021 In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 168-174 32799332-2 2021 We determined the mechanisms of ethanol-induced impaired phosphorylation of mechanistic target of rapamycin complex 1 (mTORC1) and AMP kinase (AMPK) with consequent dysregulated skeletal muscle protein homeostasis (balance between protein synthesis and breakdown). Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 119-125 33734592-7 2021 Topical application of rapamycin improved clinical symptoms in rosacea patients, suggesting mTORC1 inhibition can serve as a novel therapeutic avenue for rosacea. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 92-98 33742521-4 2021 mTORC1 activity showed the reciprocal pattern, with age-related increases blocked by Rapa, ACA, and 17aE2 (in males only). Sirolimus 85-89 CREB regulated transcription coactivator 1 Mus musculus 0-6 33635313-1 2021 The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 33571703-3 2021 It is the intention of this review to delineate potential molecular aging mechanisms related to the intake of non-fermented milk versus yogurt on the basis of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 181-190 CREB regulated transcription coactivator 1 Mus musculus 202-208 33879610-3 2021 We show that IR preferentially stimulates phosphorylations associated with mammalian target of rapamycin complex 1 (mTORC1) and Akt pathways, whereas IGF1R preferentially stimulates phosphorylations on proteins associated with the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases), and cell cycle progression. Sirolimus 95-104 CREB regulated transcription coactivator 1 Mus musculus 116-122 33574130-2 2021 Although mechanistic target of rapamycin complex 1 (mTORC1) activation enhances MM cell growth, the mTORC1 inhibitor everolimus has shown limited efficacy in clinical trials of MM patients. Sirolimus 31-40 CREB regulated transcription coactivator 1 Mus musculus 52-58 33991444-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) plays a central role in muscle protein synthesis and repeated bouts of resistance exercise (RE) blunt mTORC1 activation. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 33991444-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) plays a central role in muscle protein synthesis and repeated bouts of resistance exercise (RE) blunt mTORC1 activation. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 153-159 33910001-1 2021 Leucyl-tRNA synthetase 1 (LARS1) mediates activation of leucine-dependent mechanistic target of rapamycin complex 1 (mTORC1) as well as ligation of leucine to its cognate tRNAs, yet its mechanism of leucine sensing is poorly understood. Sirolimus 96-105 CREB regulated transcription coactivator 1 Mus musculus 117-123 33910008-1 2021 Recent studies have demonstrated that selective activation of mammalian target of rapamycin complex 1 (mTORC1) in the cerebellum by deletion of the mTORC1 upstream repressors TSC1 or phosphatase and tensin homolog (PTEN) in Purkinje cells (PCs) causes autism-like features and cognitive deficits. Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 103-109 33910008-1 2021 Recent studies have demonstrated that selective activation of mammalian target of rapamycin complex 1 (mTORC1) in the cerebellum by deletion of the mTORC1 upstream repressors TSC1 or phosphatase and tensin homolog (PTEN) in Purkinje cells (PCs) causes autism-like features and cognitive deficits. Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 148-154 34027051-2 2021 Our recent study linked cyst(e)ine availability with glutathione peroxidase 4 (GPX4) protein synthesis and ferroptosis mitigation via a Rag-mechanistic target of rapamycin complex 1 (mTORC1) axis, and proposed that co-targeting mTORC1 and ferroptosis is a promising strategy for cancer therapy. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 183-189 33910229-7 2021 Consistent with these findings, the mTORC1 inhibitor Rapamycin effectively blocks CCM formation in mouse models. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 36-42 34027051-2 2021 Our recent study linked cyst(e)ine availability with glutathione peroxidase 4 (GPX4) protein synthesis and ferroptosis mitigation via a Rag-mechanistic target of rapamycin complex 1 (mTORC1) axis, and proposed that co-targeting mTORC1 and ferroptosis is a promising strategy for cancer therapy. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 228-234 33903099-6 2021 Rapamycin and its analogs only partially inhibit mTORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 49-55 33922083-7 2021 The mTORC1 inhibitor Sirolimus is the only FDA-approved drug to treat LAM. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 33922083-10 2021 New methods successfully implicated mTORC1 inhibitors, including Sirolimus, as capable of reverting the LAM transcriptional signatures. Sirolimus 65-74 CREB regulated transcription coactivator 1 Mus musculus 36-42 33919313-1 2021 Increased amino acid availability acutely stimulates protein synthesis partially via activation of mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 121-130 CREB regulated transcription coactivator 1 Mus musculus 142-148 33881936-2 2021 The serine/threonine kinase, the mechanistic target of rapamycin complex 1 (mTORC1), also plays a fundamental role in the regulation of protein turnover and cell size, including in skeletal muscle, where mTORC1 is sufficient to increase protein synthesis and muscle fiber size, and is necessary for mechanical overload-induced muscle hypertrophy. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 76-82 33881936-2 2021 The serine/threonine kinase, the mechanistic target of rapamycin complex 1 (mTORC1), also plays a fundamental role in the regulation of protein turnover and cell size, including in skeletal muscle, where mTORC1 is sufficient to increase protein synthesis and muscle fiber size, and is necessary for mechanical overload-induced muscle hypertrophy. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 204-210 33881936-5 2021 Mechanical overload induced an increase in mTORC1 signalling, protein synthesis and muscle mass, and these were associated with rapamycin-sensitive increases in adenosylmethione decarboxylase 1 (Amd1), spermidine synthase (SpdSyn) and c-Myc. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 43-49 33923449-1 2021 Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 183-192 CREB regulated transcription coactivator 1 Mus musculus 204-210 33864571-9 2021 In the OOA model, upregulated extracellular regulated protein kinases 1/2 (ERK1/2), which can be regulated by SOCC and IP3R proteins transient receptor potential canonical 1 (TRPC1)/IP3R with elevated cytoplasmic calcium signaling, over-inhibited forkhead/winged helix O (FOXO) signaling and over-activated mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 327-336 CREB regulated transcription coactivator 1 Mus musculus 348-354 33923449-8 2021 Rapamycin efficiently decreased mTORC1 activity of these TSC1-deficient cells in vitro. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 32-38 33398329-5 2021 We demonstrate that mTORC1 phosphorylates LARP1 in vitro and in vivo, activities that are efficiently inhibited by rapamycin and torin1. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 20-26 33863987-2 2021 LARS is also essential to sensitize the intracellular leucine concentration to the mammalian target of rapamycin complex 1 (mTORC1) activation. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 124-130 33846288-2 2021 Signaling by mammalian target of rapamycin complex 1 (mTORC1) plays a central role in the maintenance of skeletal muscle mass by regulating net protein balance; yet, its role in denervation-induced atrophy is unclear. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 54-60 33897381-1 2021 Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) due to mutations in genes along the PI3K-mTOR pathway and the GATOR1 complex causes a spectrum of neurodevelopmental disorders (termed mTORopathies) associated with malformation of cortical development and intractable epilepsy. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 66-72 33368291-6 2021 Concordantly, loss of GPT2 results in an impairment of mechanistic target of rapamycin complex 1 (mTORC1) activity as well as the induction of autophagy. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 98-104 33876772-1 2021 The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 57-63 33912444-11 2021 Moreover, rapamycin, an inhibitor of mTOR complex 1 (mTORC1), downregulated BCRP expression and enhanced the effects of particular drugs, including doxorubicin and paclitaxel. Sirolimus 10-19 CREB regulated transcription coactivator 1 Mus musculus 53-59 33852892-1 2021 The activation of cap-dependent translation in eukaryotes requires multisite, hierarchical phosphorylation of 4E-BP by the 1 MDa kinase mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 156-165 CREB regulated transcription coactivator 1 Mus musculus 177-183 33476693-8 2021 Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 72-78 33476693-8 2021 Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 204-210 33476693-8 2021 Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 204-210 33476693-8 2021 Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 204-210 33471625-1 2021 Disuse-induced muscle atrophy is accompanied by a blunted postprandial response of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 107-116 CREB regulated transcription coactivator 1 Mus musculus 128-134 33977204-0 2021 Deletion of Rptor in Preosteoblasts Reveals a Role for the Mammalian Target of Rapamycin Complex 1 (mTORC1) Complex in Dietary-Induced Changes to Bone Mass and Glucose Homeostasis in Female Mice. Sirolimus 79-88 CREB regulated transcription coactivator 1 Mus musculus 100-106 33987434-3 2021 Enhanced activity of mechanistic target of rapamycin complex 1 (mTORC1) is a hallmark of HCC promoted by hepatitis B virus (HBV) and hepatitis C virus (HCV). Sirolimus 43-52 CREB regulated transcription coactivator 1 Mus musculus 64-70 33422633-4 2021 Hence, the present study aimed to better investigate these mechanisms, also considering a potential involvement of mammalian Target Of Rapamycin Complex1 (mTORC1)-ribosomal protein S6 Kinase beta1 (S6K1) pathway. Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 155-161 33244735-1 2021 Recently, it was reported that mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity during memory retrieval is required for normal expression of aversive and non-aversive long-term memories. Sirolimus 63-72 CREB regulated transcription coactivator 1 Mus musculus 84-90 33422633-8 2021 Interestingly, inhibition of mTORC1-S6K1 pathway using rapamycin significantly restored the IRS-1/Akt/eNOS activation, suggesting a feedback regulation of IRS-1/Akt signal through S6K1. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 29-35 33834258-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) is an important regulator of cellular metabolism that is commonly hyperactivated in cancer. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33883257-3 2021 METHOD: In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8+ TILs. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 136-142 33782423-4 2021 Its production is supported by mechanistic target of rapamycin complex 1 (mTORC1) and signal transducer and activator of transcription 3 (STAT3). Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 74-80 33977204-1 2021 The mammalian target of rapamycin complex 1 (mTORC1) complex is the major nutrient sensor in mammalian cells that responds to amino acids, energy levels, growth factors, and hormones, such as insulin, to control anabolic and catabolic processes. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 33515593-4 2021 Inhibition of mTORC1 with rapamycin or knockdown of raptor, regulatory-associated protein of mTORC1, with shRNA dramatically rescued the cells from Bort-caused apoptosis. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 14-20 33561653-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) signaling is the prototypical pathway regulating protein synthesis and cell proliferation. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33741392-6 2021 This excessive division could be completely blocked by the mTORC1 inhibitor rapamycin. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 59-65 33707434-5 2021 Mechanistically, we find that cyst(e)ine activates mechanistic/mammalian target of rapamycin complex 1 (mTORC1) and promotes GPX4 protein synthesis at least partly through the Rag-mTORC1-4EBP signaling axis. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 104-110 33347604-1 2021 BACKGROUND AND PURPOSE: Cannabidiol (CBD) has been shown to differentially regulate the mechanistic target of rapamycin complex 1 (mTORC1) in preclinical models of disease, where it reduces activity in models of epilepsies and cancer and increases it in models of multiple sclerosis (MS) and psychosis. Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 131-137 33694218-3 2021 Rheb is a small GTPase which, when bound to GTP, activates mechanistic target of rapamycin complex 1 (mTORC1), a protein kinase that drives anabolic processes including protein synthesis and ribosome biogenesis. Sirolimus 81-90 CREB regulated transcription coactivator 1 Mus musculus 102-108 33656206-2 2021 The pharmacologically interesting mechanistic Target of Rapamycin Complex1 (mTORC1) is a central regulator of cellular growth and metabolism and a causative role has been attributed for a number of inflammatory pathologies such as psoriasis1,2 . Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 76-82 33626233-4 2021 BC cell-intrinsic PD-L1 promoted mammalian target of rapamycin complex 1 (mTORC1) signals in vitro and augmented in vivo immune-independent cell growth and metastatic cancer spread, similar to effects we reported in melanoma and ovarian cancer. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 74-80 33626233-6 2021 BC cell-intrinsic PD-L1 also mediated chemotherapy resistance to the commonly used BC chemotherapy agents cis-platinum and gemcitabine and to the mTORC1 inhibitor, rapamycin. Sirolimus 164-173 CREB regulated transcription coactivator 1 Mus musculus 146-152 33132009-7 2021 Immunoblot assays showed the expected inhibition of complex 1 of mechanistic or mammalian target of rapamycin (mTORC1) and effectors (S6K rpS6 and S6K eEF2K eEF2) in colon by lifelong rapamycin treatments. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 111-117 33132009-9 2021 CONCLUSION: These data indicate that enteric rapamycin prevents or delays colon neoplasia in ApcMin/+-DSS mice through inhibition of mTORC1 in the crypt cells. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 133-139 33718332-0 2020 Rapamycin-Loaded Lipid Nanocapsules Induce Selective Inhibition of the mTORC1-Signaling Pathway in Glioblastoma Cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 71-77 33646118-1 2021 The mechanistic target of rapamycin complex 1 (mTORC1) stimulates a coordinated anabolic program in response to growth-promoting signals. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33524531-3 2021 It is well established that REDD1 mediates the cellular response to a number of diverse stressors through repression of the central metabolic regulator known as mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 183-192 CREB regulated transcription coactivator 1 Mus musculus 204-210 32956517-7 2021 Moreover, the THC-mediated modulation of oligodendroglial differentiation relied on the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, as mTORC1 pharmacological inhibition prevented the THC effects. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 147-153 32956517-7 2021 Moreover, the THC-mediated modulation of oligodendroglial differentiation relied on the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, as mTORC1 pharmacological inhibition prevented the THC effects. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 177-183 33660929-2 2021 In particular, mTOR complex 1 (mTORC1) promotes protein synthesis in ribosomes by activating the downstream effectors, p70S6K and 4EBP1, in skeletal muscle and is highly sensitive to rapamycin, an mTOR inhibitor. Sirolimus 183-192 CREB regulated transcription coactivator 1 Mus musculus 31-37 33673489-3 2021 Thus, we investigated the influence of pre-treatment with rapamycin, an mTORC1 inhibitor, on the development of recognition memory deficits in adult rats that were neonatally exposed to ethanol. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 72-78 32037974-1 2021 Rapamycin and their derivatives known as rapalogs, were the first-generation mTOR inhibitors which interacted with mTORC1 but not with the mTORC2 protein. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 115-121 33279634-4 2021 Rapamycin (a selective mTORC1 inhibitor, 0.2 nmol/site, i.c.v.) Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 23-29 33718332-9 2020 Nevertheless, it demonstrated the selective inhibition of the phosphorylation of mTORC1 signaling pathway on Ser2448 at a concentration of 1 muM rapamycin in serum-free medium. Sirolimus 145-154 CREB regulated transcription coactivator 1 Mus musculus 81-87 33708210-6 2021 Mechanistically, we unravel that IL-10 activates the mammalian target of rapamycin complex 1 (mTORC1) to regulate metabolic reprogramming in human NK cells. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 94-100 33671526-4 2021 In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 74-80 33671526-4 2021 In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 224-230 33602225-2 2021 The E3 ubiquitin ligase RNF152 has been reported to regulate the activity of the mechanistic target of rapamycin complex 1 (mTORC1), induce autophagy and apoptosis. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 124-130 33482580-2 2021 Mutations in the TSC2 gene and loss of TSC2 promote cell growth by the mammalian target of rapamycin complex 1 (mTORC1) activation. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 33679734-7 2021 More importantly, rapamycin (a specific mTORC1 inhibitor) significantly restored the expression of cell-junction proteins and exerted a protective effect on the BTB during UPEC infection. Sirolimus 18-27 CREB regulated transcription coactivator 1 Mus musculus 40-46 33731662-3 2021 The role of RT-induced anabolic stimulation was investigated in tumor-bearing rats with the mTORC1 inhibitor rapamycin, and cross-sectional areas of skeletal muscle were evaluated to identify atrophy or hypertrophy. Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 92-98 33599151-6 2021 mTOR forms two protein complexes, mTORC1, which is sensitive to rapamycin and mTORC2, which is not directly inhibited by this drug. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 34-40 33599151-7 2021 Rapamycin has facilitated the discovery of the various functions of mTORC1 in metabolism. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 68-74 33672955-6 2021 In addition, Octpep-1 combined with rapamycin (mTORC1 inhibitor) or LY3214996 (ERK1/2 inhibitor) augmented the cytotoxicity against BRAF(V600E) melanoma cells in comparison with the inhibitors or Octpep-1 alone. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 47-53 33597177-4 2021 Notably, the rapamycin-sensitive mTORC1 pathway, rather than the rapamycin-insensitive mTORC2 pathway, was responsible for elevated activation of RIPK1, RIPK3, and MLKL in TSC1-deficient macrophages. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 33-39 33593593-2 2021 It is tightly regulated by a suite of kinases responsive to nutrient status, including mammalian target of rapamycin complex 1 (mTORC1), AMP-activated protein kinase (AMPK), protein kinase C-alpha (PKCalpha), MAPK-activated protein kinases 2/3 (MAPKAPK2/3), Rho kinase 1 (ROCK1), c-Jun N-terminal kinase 1 (JNK), and Casein kinase 2 (CSNK2). Sirolimus 107-116 CREB regulated transcription coactivator 1 Mus musculus 128-134 33497611-3 2021 They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Sirolimus 191-200 CREB regulated transcription coactivator 1 Mus musculus 212-218 33744643-7 2021 A protein x citrulline interaction was observed for some plasma and muscle AA levels with a significant activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling suggesting higher anabolism with the combination of citrulline and lactoserum. Sirolimus 140-149 CREB regulated transcription coactivator 1 Mus musculus 161-167 33574709-2 2021 Inhibition of mTORC1 (mechanistic target of rapamycin complex 1) activity upon aspirin treatment has been reported in breast cancer cells harboring PI3KCA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) mutation and is considered to account for anticancer action. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 14-20 33285244-4 2021 We used leucine and rapamycin to modulate mTORC1 activation and evaluate this effect on circadian rhythms. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 42-48 33285244-9 2021 Inhibition of liver mTORC1 by leucine or rapamycin led to low-amplitude circadian rhythms. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 20-26 33508145-13 2021 By inhibiting p53 alone or both mTORC1 and p53 with rapamycin and a p53 inhibitor, we elucidated that p53 acts downstream of mTORC1 and that mTORC1 thereby promotes odontoblast mineralization. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 125-131 33165974-2 2021 Extensive studies have attributed the lysosomal localization of the mechanistic target of rapamycin complex 1 (mTORC1) during its activation. Sirolimus 90-99 CREB regulated transcription coactivator 1 Mus musculus 111-117 33284085-10 2021 In H4IIE cells, expression of a 4E-BP1 variant that is unable to be phosphorylated by mTORC1 or suppression of mTORC1 with rapamycin attenuated activity of a luciferase reporter encoding the Rbp4 mRNA 5"-untranslated region (UTR). Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 111-117 33277337-6 2021 mRNA expression analysis and differential proteomics on betaFurKO islets revealed activation of Activating Transcription Factor 4 (ATF4), which was mediated by mammalian target of rapamycin C1 (mTORC1). Sirolimus 180-189 CREB regulated transcription coactivator 1 Mus musculus 194-200 33508145-13 2021 By inhibiting p53 alone or both mTORC1 and p53 with rapamycin and a p53 inhibitor, we elucidated that p53 acts downstream of mTORC1 and that mTORC1 thereby promotes odontoblast mineralization. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 125-131 33665645-2 2021 Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) has been shown to delay or reverse many age-related phenotypes, including declining immune function. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 61-67 33451752-8 2021 Further mechanistic study uncovered that inhibition of mTORC1 with rapamycin blocked BV-induced ER stress, and treatment with Sestrin2 siRNA blocked the inhibition effect of AMPK to mTORC1. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 55-61 33665645-3 2021 Rapamycin (sirolimus) and rapamycin derivatives are US Food and Drug Administration-approved inhibitors of mTORC1 with broad clinical utility and well established dosing and safety profiles. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 107-113 33665645-3 2021 Rapamycin (sirolimus) and rapamycin derivatives are US Food and Drug Administration-approved inhibitors of mTORC1 with broad clinical utility and well established dosing and safety profiles. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 107-113 33665645-3 2021 Rapamycin (sirolimus) and rapamycin derivatives are US Food and Drug Administration-approved inhibitors of mTORC1 with broad clinical utility and well established dosing and safety profiles. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 107-113 33340488-5 2021 Consequently, expression of the serine biosynthesis enzyme PHGDH was required for sensitivity to the mTORC1 inhibitor rapamycin in breast-cancer-derived lung tumors, but not in primary breast tumors. Sirolimus 118-127 CREB regulated transcription coactivator 1 Mus musculus 101-107 33272830-1 2021 Autophagy and cap-dependent mRNA translation are tightly regulated by the mechanistic target of rapamycin complex 1 (mTORC1) signalling complex in response to nutrient availability. Sirolimus 96-105 CREB regulated transcription coactivator 1 Mus musculus 117-123 33307091-1 2021 The Tuberous Sclerosis Complex (TSC) protein complex (TSCC), comprising TSC1, TSC2, and TBC1D7, is widely recognised as a key integration hub for cell growth and intracellular stress signals upstream of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 227-236 CREB regulated transcription coactivator 1 Mus musculus 248-254 33503424-5 2021 Using metabolomic and lipidomic profiling, cellular response to PHGDH inhibition is identified as accumulation of unsaturated lipids, branched chain amino acids, and methionine cycle intermediates, leading to activation of pro-survival mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 256-265 CREB regulated transcription coactivator 1 Mus musculus 277-283 33483593-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic beta-cells leads to diabetes. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 33340489-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and proliferation by sensing fluctuations in environmental cues such as nutrients, growth factors, and energy levels. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 33237838-5 2021 Using pHLARE we show decreased pHlys with inhibiting activity of the mammalian target of rapamycin complex 1 (mTORC1), in breast, pancreatic, colon, and glioblastoma cancer cells compared with untransformed cells, and with the activated oncogenes H-RasV12 and R-RasV12. Sirolimus 89-98 CREB regulated transcription coactivator 1 Mus musculus 110-116 33527023-1 2021 The present study aimed to investigate the role of mammalian target of rapamycin complex 1 (mTORC1) in the remodeling of the condyle subchondral bone in rats with temporomandibular joint osteoarthritis (TMJ OA) and explore the mechanisms involved. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 92-98 33527023-10 2021 The mTORC1 pathway was inhibited by a local injection of rapamycin, and the number of osteoblasts and mRNA levels of osteogenic markers in the condyle subchondral bone decreased, but the number of osteoclasts was basically unchanged. Sirolimus 57-66 CREB regulated transcription coactivator 1 Mus musculus 4-10 33189863-4 2021 It activated mammalian target of rapamycin complex 1 (mTORC1) and suppressed autophagy in glomeruli of fructose-fed rats and in fructose-exposed conditionally immortalized human podocytes (HPCs). Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 54-60 33542926-3 2021 To examine the role of mechanistic target of rapamycin complex 1 (mTORC1) on amino acid catabolism, mTORC1 was inactivated by rapamycin or shRNA targeting Raptor, versus activated by overexpressing Rheb or amino acids in human hepatocytes. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 66-72 33542926-3 2021 To examine the role of mechanistic target of rapamycin complex 1 (mTORC1) on amino acid catabolism, mTORC1 was inactivated by rapamycin or shRNA targeting Raptor, versus activated by overexpressing Rheb or amino acids in human hepatocytes. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 100-106 33442914-5 2022 Akt acts by activating mechanistic target of rapamycin complex 1 (mTORC1) and by arresting autophagic gene expression. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 66-72 33597869-2 2020 Antigen-induced T-cell proliferation via mTORC1 suppressed by Rapamycin has been used to improve SLE primarily. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 41-47 33519806-6 2020 Our data indicated that Arg1 haploinsufficiency promoted Abeta deposition, exacerbated some behavioral impairment, and decreased components of Ragulator-Rag complex involved in mechanistic target of rapamycin complex 1 (mTORC1) signaling and autophagy. Sirolimus 199-208 CREB regulated transcription coactivator 1 Mus musculus 220-226 33597869-11 2020 INK128 effectively suppressed mTORC1 and mTORC2 activity in T cells, but rapamycin just suppressed mTORC1 activity. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 99-105 33052068-3 2021 The mechanistic target of rapamycin complex 1 (mTORC1) pathway integrates external and internal signals, including those by amino acids (AAs), to promote normal preimplantation development. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33432187-1 2021 Rapid antidepressants are novel treatments for major depressive disorder (MDD) and work by blocking N-methyl-D-aspartate receptors (NMDARs), which, in turn, activate the protein synthesis pathway regulated by mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 241-250 CREB regulated transcription coactivator 1 Mus musculus 262-268 33429026-3 2021 In this context, the activity of the mechanistic Target Of Rapamycin Complex 1 (mTORC1) is of major importance. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 80-86 33511116-5 2020 In this review, we will systematically summarize the recent progress of amino acid metabolism in malignancy and discuss their interconnection with mammalian target of rapamycin complex 1 (mTORC1) signaling, epigenetic modification, tumor growth and immunity, and ferroptosis. Sirolimus 167-176 CREB regulated transcription coactivator 1 Mus musculus 188-194 33485108-3 2021 According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker. Sirolimus 107-116 CREB regulated transcription coactivator 1 Mus musculus 128-134 33398801-1 2021 Tuberous sclerosis complex (TSC) is a dominant autosomal genetic disorder caused by loss-of-function mutations in TSC1 and TSC2, which lead to constitutive activation of the mammalian target of rapamycin C1 (mTORC1) with its decoupling from regulatory inputs. Sirolimus 194-203 CREB regulated transcription coactivator 1 Mus musculus 208-214 32755490-5 2021 However, it has been hypothesised that mammalian target of rapamycin complex 1 (mTORC1) hyperactivation in the presence of amino acid overload contributes to reduced insulin-stimulated glucose uptake due to insulin receptor substrate (IRS) degradation and reduced Akt-AS160 activity. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 80-86 31541182-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) regulates CD8+ T-cell differentiation and function. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 33040459-7 2021 In Ba/F3 cells transformed by NPM-ALK and Ki-JK cells, p53 activation induced by knockdown of EBP2 was significantly inhibited by Akt inhibitor GDC-0068, mTORC1 inhibitor rapamycin, and knockdown of Raptor, an essential component of mTORC1. Sirolimus 171-180 CREB regulated transcription coactivator 1 Mus musculus 154-160 33356791-6 2021 Importantly, inhibition of mTORC1 signaling either by the mTORC1 inhibitor rapamycin or by knockdown of Raptor, a unique component of mTORC1, during palbociclib treatment of CAMA1 cells blocks the induction of complete senescence. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 27-33 32394479-3 2021 The mTOR protein is incorporated into two distinct complexes: mammalian target of Rapamycin complex 1 (mTORC1) and mammalian target of Rapamycin complex 2 (mTORC2). Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 103-109 32583421-7 2021 Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARalpha, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells. Sirolimus 149-158 CREB regulated transcription coactivator 1 Mus musculus 184-190 32474911-7 2020 Furthermore, our mechanistic studies unveiled that the SLC34a1-CreERT2 recombinase-mediated Pik3c3 downregulation inhibited UNX- or amino acid-stimulated lysosomal localization and signaling activation of mechanistic target of rapamycin complex 1 (mTORC1) in the renal proximal tubules. Sirolimus 227-236 CREB regulated transcription coactivator 1 Mus musculus 248-254 33375025-1 2020 The mechanistic target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33299044-6 2020 Furthermore, the suppression of Fgf23 expression by PTEN knockdown or insulin simulation in UMR106 cells was partially restored by the treatment with the mTORC1 inhibitor, rapamycin. Sirolimus 172-181 CREB regulated transcription coactivator 1 Mus musculus 154-160 33273014-2 2021 Previously we established NF2 loss activates mechanistic target of rapamycin complex 1 (mTORC1) and mTORC2 signaling, leading to clinical trials for NF2 and meningioma. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 88-94 33171062-6 2020 Mechanistically, curcumin inactivates the mechanistic target of rapamycin complex 1 (mTORC1), the upstream regulator of rDNA transcription and autophagy induction, by inhibiting mTOR lysosomal localization. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 85-91 32722876-1 2020 Mechanistic target of rapamycin complex 1 (mTORC1) functions as regulating different cellular processes, including cell growth, proliferation, motility, survival, metabolism, autophagy, and protein transcription. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 33222863-1 2020 Different models of lactation offer conflicting evidence as to whether insulin signaling is required for AA to stimulate mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 143-152 CREB regulated transcription coactivator 1 Mus musculus 164-170 32848049-6 2020 Using Western blot analysis and AMP/ATP measurements, we found that simvastatin treatment blocked activation of mechanistic target of rapamycin complex 1 (mTORC1), activated AMP-activated protein kinase (AMPK) through increased intracellular AMP:ATP ratios, and favored nuclear translocation of transcription factor EB (TFEB). Sirolimus 134-143 CREB regulated transcription coactivator 1 Mus musculus 155-161 32893874-6 2020 Previous studies showed that the mechanistic target of rapamycin complex 1 (mTORC1) inhibition suppressed the early but not late muscle protein synthesis-response, while the inhibition of both mTORC1 and mTORC2 abolished both effects. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 76-82 32893874-10 2020 Vehicle or the mTORC1 inhibitor rapamycin (1.5 mg/kg) was injected intraperitoneally 1 h before contraction. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 15-21 32893874-14 2020 In rapamycin-treated Rictor mKO mice, the same mTORC1 signalling was blocked following contractions. Sirolimus 3-12 CREB regulated transcription coactivator 1 Mus musculus 47-53 32893874-15 2020 Our results indicate that although neither rapamycin-sensitive mTOR/mTORC1 nor mTORC2 regulates contraction-induced muscle protein synthesis, combined inhibition of rapamycin-sensitive mTOR/mTORC1 and mTORC2 synergistically inhibits contraction-induced muscle protein synthesis. Sirolimus 165-174 CREB regulated transcription coactivator 1 Mus musculus 190-196 33243998-4 2020 Mechanistically, ISO inhibits AKT as well as, downstream of AKT, the mechanistic target of rapamycin complex 1 (mTORC1), coupled to the activation of the pro-autophagic transcription factors EB (TFEB) and E3 (TFE3). Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 32666288-1 2020 Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. Sirolimus 61-70 CREB regulated transcription coactivator 1 Mus musculus 86-92 33256738-14 2020 The pyroptosic effect by S. aureus infection was promoted by either rapamycin or Stattic, a specific inhibitor for mTORC1 or STAT3. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 115-121 33257668-1 2020 The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth, nutrient and energy status cues to control cell growth and metabolism. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33324640-1 2020 Mechanistic Target of Rapamycin Complex 1 (mTORC1) serves as positive regulator of placental nutrient transport and mitochondrial respiration. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 33319180-5 2020 Rapamycin inhibited mTORC1 and PTEN, but augmented mTORC2 with restoration of miRNA-302a under diabetic conditions. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 20-26 33319180-7 2020 We conclude that rapamycin attenuates reperfusion injury in diabetic heart through inhibition of PTEN and mTORC1 with restoration of miR-302a-mTORC2 signaling. Sirolimus 17-26 CREB regulated transcription coactivator 1 Mus musculus 106-112 32878988-12 2020 Pretreating cells with mTORC1 inhibitor rapamycin restored BCKAs effect on insulin-induced AKT phosphorylation. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 23-29 33238127-6 2020 However, conventional type 2 dendritic cells (cDC2) and T cell functions of mammalian target of rapamycin complex 1 (mTORC1) increase effector precursor induction while decreasing the proportion of T cells that can become peripheral Foxp3+ regulatory T (pTreg) cells. Sirolimus 96-105 CREB regulated transcription coactivator 1 Mus musculus 117-123 33157014-1 2020 Amino-acid-induced lysosomal mechanistic target of rapamycin complex 1 (mTORC1) localization through the Rag GTPases is a critical step for its activation by Rheb GTPase. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 72-78 33187130-3 2020 The mammalian target of Rapamycin Complex 1 (mTORC1) is a major functional axis regulating various aspects of cellular growth and metabolism. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 33292704-6 2020 Milk protein synthesis is governed at mammary level by a set of transduction pathways, including the mechanistic target of rapamycin complex 1 (mTORC1), the integrated stress response (ISR), and the unfolded protein response (UPR). Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 144-150 33171588-3 2020 Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 32977361-12 2020 Meanwhile, the oncogenic effect of BUB1B will be impaired when the mTORC1 signaling pathway was inhibited by rapamycin. Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 67-73 31738412-10 2020 In addition, RAPA restored AKT phosphorylation (target of mTORC2), but suppressed S6 phosphorylation (target of mTORC1) following I/R injury. Sirolimus 13-17 CREB regulated transcription coactivator 1 Mus musculus 112-118 32668192-8 2020 Rapamycin, which incompletely and allosterically inhibits mTORC1, had no effect on TGF-beta-mediated induction of ATF4; however, Rapalink-1, which specifically targets the kinase domain of mTORC1, completely inhibited ATF4 induction and metabolic reprogramming downstream of TGF-beta. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 189-195 32567791-1 2020 BACKGROUND: Recently, insulin-like growth factor-1 (IGF-1), forkhead box transcription factor (Fox) O1, and mechanistic target of rapamycin complex 1 (mTORC1) signalling have been introduced as key elements in acne pathogenesis. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 151-157 32558194-8 2020 Co-treatment of GABA with an inhibitor specific for PI3K, mTORC1/2, or p70S6K (via wortmannin, rapamycin, or PF-4708671, respectively) abolished GABA-stimulated beta-cell proliferation in mouse and human islets. Sirolimus 95-104 CREB regulated transcription coactivator 1 Mus musculus 58-64 32810332-1 2020 AKT-mTORC1 (mammalian target of rapamycin complex 1) signaling pathway plays a critical role in tumorigenesis and can be targeted by rapamycin. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 4-10 33097830-6 2020 Mechanistically, we find that L-arginine stimulates Wnt2b secretion by CD90+ stromal cells through the mammalian target of rapamycin complex 1 (mTORC1) and that blocking Wnt2b production prevents L-arginine-induced ISC expansion. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 144-150 33076974-2 2020 It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 89-95 33009372-6 2020 To confirm the observations of the genetic approach, we used a pharmacological method and determined that the mTORC1 inhibitor rapamycin has a profound influence upon post-synaptic D2R-dependent functions. Sirolimus 127-136 CREB regulated transcription coactivator 1 Mus musculus 110-116 32871684-1 2020 BACKGROUND: Recent studies have suggested the role of mammalian target of rapamycin complex 1 (mTORC1) in the pathophysiology of depression. Sirolimus 74-83 CREB regulated transcription coactivator 1 Mus musculus 95-101 32871684-7 2020 RESULT: Our results showed that the decreasing effects of CUMS and CSDS on the mTORC1 signaling cascade in the hippocampus and mPFC were restored by venlafaxine, and the use of rapamycin, LY294002, U0126 and mTORC1-shRNA fully abolished the anti-stress actions of venlafaxine in mice. Sirolimus 177-186 CREB regulated transcription coactivator 1 Mus musculus 79-85 32862047-2 2020 The mammalian target of rapamycin complex 1 (mTORC1) is a negative regulator of autophagy, but its role in Cd-induced autophagy inhibition and possible regulatory mechanisms remains poorly understood. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 32862047-5 2020 Importantly, Cd exposure triggered the recruitment of mTORC1 onto lysosome membrane assessed by immunofluorescence co-localization analysis, which was obviously inhibited by rapamycin or torin 1. Sirolimus 174-183 CREB regulated transcription coactivator 1 Mus musculus 54-60 32901865-3 2020 Proline rich polypeptide 1 (PRP-1), which is a 15-amino acid inhibitor of mammalian target of rapamycin complex-1 (mTORC1), has been indicated to exert cytostatic and immunomodulatory properties in human chondrosarcoma cells in a monolayer. Sirolimus 94-103 CREB regulated transcription coactivator 1 Mus musculus 115-121 32716476-1 2020 Sirolimus, also known as rapamycin, and its closely-related rapamycin analog (rapalog) Everolimus inhibit "mammalian target of rapamycin complex 1" (mTORC1), whose activity is required for spermatogenesis. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 149-155 32716476-1 2020 Sirolimus, also known as rapamycin, and its closely-related rapamycin analog (rapalog) Everolimus inhibit "mammalian target of rapamycin complex 1" (mTORC1), whose activity is required for spermatogenesis. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 149-155 32716476-1 2020 Sirolimus, also known as rapamycin, and its closely-related rapamycin analog (rapalog) Everolimus inhibit "mammalian target of rapamycin complex 1" (mTORC1), whose activity is required for spermatogenesis. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 149-155 32716476-1 2020 Sirolimus, also known as rapamycin, and its closely-related rapamycin analog (rapalog) Everolimus inhibit "mammalian target of rapamycin complex 1" (mTORC1), whose activity is required for spermatogenesis. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 149-155 33060361-1 2020 The mechanistic target of rapamycin complex 1 (mTORC1) couples nutrient sufficiency to cell growth. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 32460327-1 2020 The two primary molecular regulators of lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 95-104 CREB regulated transcription coactivator 1 Mus musculus 116-122 33046706-4 2020 We show that lack of CTSD impaired mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling and induced reversible cellular quiescence. Sirolimus 57-66 CREB regulated transcription coactivator 1 Mus musculus 78-84 32480429-10 2020 Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II. Sirolimus 65-74 CREB regulated transcription coactivator 1 Mus musculus 48-54 32761379-4 2020 The identification of TSC1 and TSC2, as tumor suppressor genes causative of the disorder, led to the elucidation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and its pivotal role in the pathogenesis of hamartoma formation. Sirolimus 140-149 CREB regulated transcription coactivator 1 Mus musculus 161-167 32761379-5 2020 This knowledge was translated into standard clinical practice with the discovery of rapamycin, and additional analogues, as inhibitors of mTORC1. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 138-144 32587106-2 2020 Unchecked PI3K pathway signaling increases activation of the mechanistic target of rapamycin complex 1 (mTORC1), which promotes tumorigenicity. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 104-110 33038070-2 2020 The mechanistic target of rapamycin complex 1 (mTORC1) and its upstream protein kinase Akt1 have been implicated as a central signaling pathway that regulates protein synthesis in the skeletal muscle; however, the precise molecular regulation of mTORC1 activity is largely unknown. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 33038070-2 2020 The mechanistic target of rapamycin complex 1 (mTORC1) and its upstream protein kinase Akt1 have been implicated as a central signaling pathway that regulates protein synthesis in the skeletal muscle; however, the precise molecular regulation of mTORC1 activity is largely unknown. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 246-252 32480256-1 2020 OBJECTIVES: Resistance training combined with consumption of a high-protein diet (HPD) is typically recommended to increase muscle mass, as both acute resistance exercise (RE) and dietary protein intake stimulate mechanistic target of rapamycin complex 1 (mTORC1) and muscle protein synthesis (MPS). Sirolimus 235-244 CREB regulated transcription coactivator 1 Mus musculus 256-262 32810332-10 2020 Our results demonstrated the lncRNA EPIC1 expression activated the AKT-mTORC1 signaling pathway through Myc and led to rapamycin resistance in breast and ovarian cancer. Sirolimus 119-128 CREB regulated transcription coactivator 1 Mus musculus 71-77 32999282-2 2020 Lysosomes also serve as signaling hubs to monitor the intracellular levels of nutrients and energy by acting as platforms for the assembly of multiple signaling pathways, such as mammalian target of rapamycin complex 1 (mTORC1) and adenosine 5"-monophosphate (AMP)-activated protein kinase (AMPK). Sirolimus 199-208 CREB regulated transcription coactivator 1 Mus musculus 220-226 33178015-7 2020 Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3-kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 77-83 32978410-1 2020 The mammalian Target of Rapamycin complex 1 (mTORC1) nutrient-sensing pathway is a central regulator of cell growth and metabolism and is dysregulated in diabetes. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 32974014-5 2020 Mechanistically, formate induces mechanistic target of rapamycin complex 1 (mTORC1) activity as quantified by phosphorylation of its targets S6, 4E-BP1, S6K1 and CAD. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 76-82 32879008-1 2020 Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 144-150 32974014-6 2020 Treatment with the allosteric mTORC1 inhibitor rapamycin abrogates CAD phosphorylation and pyrimidine synthesis induced by formate. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 30-36 32920594-5 2020 Blocking mTORC1 signal with rapamycin alleviated the neuropathic pain and restored morphine efficacy in CCI model. Sirolimus 28-37 CREB regulated transcription coactivator 1 Mus musculus 9-15 32934076-3 2020 Selected chemical and genetic perturbations in this screening platform, including rapamycin treatment and genetic ablation of the Ragulator subunit LAMTOR4, revealed the known core mTORC1 regulatory signaling complexes and the intimate interplay of the mTORC1 pathway with lysosomal function, validating the approach. Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 181-187 32693673-10 2020 Mechanistically, LAPTM4B regulated the activity of mammalian target of rapamycin complex 1 (mTORC1) via interacting with mTOR through its EC3 domain. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 92-98 33013932-3 2020 Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Sirolimus 219-228 CREB regulated transcription coactivator 1 Mus musculus 202-208 33013932-3 2020 Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Sirolimus 219-228 CREB regulated transcription coactivator 1 Mus musculus 249-255 32912327-7 2020 TLR5-mediated microglial function involves the PI3K/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway, as specific inhibitors of this signaling pathway abolish microglial activation. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 97-103 32920594-8 2020 In spinal slice recording, CCI increased the firing frequency of neurons expressing HCN channels; inhibition of mTORC1 with rapamycin could reverse the increased spinal neuronal activity in neuropathic pain. Sirolimus 124-133 CREB regulated transcription coactivator 1 Mus musculus 112-118 32906669-8 2020 Therefore, protein administration plus IL effectively prevented skeletal muscle atrophy induced by disuse, potentially via enhanced activation of targets downstream of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 209-215 32694311-1 2020 We recently reported that upregulation of the constitutively active ras homolog enriched in brain [Rheb(S16H)], which induces the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, can protect adult neurons, mediated by the induction of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), in animal models of neurodegenerative diseases. Sirolimus 168-177 CREB regulated transcription coactivator 1 Mus musculus 189-195 32908143-4 2020 We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 28-34 32826333-8 2020 Finally, using the mTORC1 inhibitor rapamycin, we demonstrate that LIN28B promotes supporting cell plasticity in an mTORC1-dependent manner. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 19-25 32779245-2 2020 Several data support the involvement of the mammalian target of rapamycin complex 1 (mTORC1) signaling in the interplay between androgens, insulin, insulin-like growth factor (IGF1), and high glycemic index diet in acne. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 85-91 32640907-7 2020 mTORC1 inhibition by nicotine or rapamycin promoted lysosomal exocytosis and CTSS secretion. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 0-6 32599128-6 2020 Inhibition of mTORC1 with rapamycin reversed the deficits of insulin signaling associated kinases activity, decreased levels of AGEs and AD-like tau phosphorylation, and also improved memory deficit in both STZ mice. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 14-20 32621956-2 2020 Multiple experimental studies have highlighted the role of increased mammalian target of rapamycin complex 1 (mTORC1) and reduced AMP-activated protein kinase (AMPK) signaling in modulating cyst growth in ADPKD. Sirolimus 89-98 CREB regulated transcription coactivator 1 Mus musculus 110-116 32765763-8 2020 In COPD, cell senescence is linked to the activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 97-103 32715871-2 2020 We previously mapped a late G1 cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G1 checkpoint known as the Restriction point. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 121-127 32721041-3 2020 As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 81-87 32721041-3 2020 As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 171-177 32495040-2 2020 Several reports have demonstrated that mitogen-activated protein kinases 3 and 1 (MAPK3/1)-mammalian target of rapamycin complex 1 (mTORC1) signaling in pre-granulosa cells promotes primordial follicle activation by increasing KIT ligand (KITL) expression and then stimulating phosphatidylinositol 3 kinase signaling in oocytes. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 132-138 32495040-6 2020 Western blotting results demonstrated that both the MAPK3/1 inhibitor U0126 and mTORC1 inhibitor rapamycin significantly decreased the levels of phosphorylated CREB, indicating that MAPK3/1-mTORC1 signaling is required for CREB activation. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 80-86 32495040-6 2020 Western blotting results demonstrated that both the MAPK3/1 inhibitor U0126 and mTORC1 inhibitor rapamycin significantly decreased the levels of phosphorylated CREB, indicating that MAPK3/1-mTORC1 signaling is required for CREB activation. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 190-196 32739207-2 2020 As an important negative regulatory factor of the mammalian target of rapamycin complex 1 (mTORC1) signal, tuberous sclerosis complex 1 (Tsc1) is also a key regulatory point of glycolysis. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 91-97 32030764-4 2020 The BCAA mimic satiety to inhibit autophagy via mechanistic targets of rapamycin complex 1 (mTORC1) activation and, in contrast, their catabolism supplements de novo lipogenesis for the formation of autophagosome membranes. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 92-98 32739207-6 2020 Prior incubation with rapamycin inhibited mTORC1 activation and abolished the enhanced glycolysis and tubular epithelial cell proliferation. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 42-48 32719541-1 2020 The mechanistic target of rapamycin complex 1 (mTORC1) kinase regulates cell growth by setting the balance between anabolic and catabolic processes. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 32612235-1 2020 The mechanistic target of rapamycin complex 1 (mTORC1) is a key metabolic hub that controls the cellular response to environmental cues by exerting its kinase activity on multiple substrates1-3. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 32736702-3 2020 In the present study, using cultured ARPE-19 cells, we determined that TGF-beta initiates a signaling pathway through extracellular signal-regulated kinase (ERK)-mammalian target of rapamycin complex 1 (mTORC1) that stimulates trans-differentiation and fibrosis of retinal pigment epithelium. Sirolimus 182-191 CREB regulated transcription coactivator 1 Mus musculus 203-209 32601986-0 2020 The mTORC1 inhibitor rapamycin and the mTORC1/2 inhibitor AZD2014 impair the consolidation and persistence of contextual fear memory. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 32863202-1 2020 Sestrin2 (Sesn2) is a stress sensor for the mammalian target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 85-91 32759469-1 2020 While the growth factors like insulin initiate a signaling cascade to induce conformational changes in the mechanistic target of rapamycin complex 1 (mTORC1), amino acids cause the complex to localize to the site of activation, the lysosome. Sirolimus 129-138 CREB regulated transcription coactivator 1 Mus musculus 150-156 33042258-6 2020 Results: Our screen identified the inhibitors of mammalian target of rapamycin complex 1 (mTORC1), which increased cell uptake of [177Lu]Lu-PP-F11N. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 90-96 32799865-1 2020 The mechanistic target of rapamycin complex 1 (mTORC1) is an essential regulator of cell growth and metabolism through the modulation of protein and lipid synthesis, lysosome biogenesis, and autophagy. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 32807195-5 2020 Although mTORC1 inhibitor rapamycin and Rapalogs have demonstrated exciting results in the recent clinical trials, however, tumors rebound and upon the discontinuation of the mTORC1 inhibition. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 9-15 32807195-5 2020 Although mTORC1 inhibitor rapamycin and Rapalogs have demonstrated exciting results in the recent clinical trials, however, tumors rebound and upon the discontinuation of the mTORC1 inhibition. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 175-181 32820315-5 2020 Moreover, we also analyzed the potential role of LeuRS in activation of mammalian target of rapamycin complex 1 (mTORC1) signaling transduction pathway in response to anabolic stimuli such as exercise and amino acids ingestion. Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 113-119 32703435-7 2020 The promoting effects of PCYT1A silencing on cell proliferation and migration could be abolished when mTORC1 signaling was inhibited by rapamycin or RAPTOR depletion. Sirolimus 136-145 CREB regulated transcription coactivator 1 Mus musculus 102-108 32824248-1 2020 The constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) leads to the overproduction of apoB-containing triacylglycerol-rich lipoproteins in HepG2 cells. Sirolimus 57-66 CREB regulated transcription coactivator 1 Mus musculus 78-84 32908958-1 2020 Background: The mechanistic target of rapamycin complex 1 (mTORC1) is a nutrient-sensing pathway and a key regulator of amino acid and glucose metabolism. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 59-65 32588887-2 2020 TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 151-157 32848709-0 2020 Rapamycin, by Inhibiting mTORC1 Signaling, Prevents the Loss of Striatal Bidirectional Synaptic Plasticity in a Rat Model of L-DOPA-Induced Dyskinesia. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 25-31 32848709-5 2020 In addition, within striatum, ERK1/2 is also able to modulate in a D1 receptor-dependent manner the activity of the mammalian target of rapamycin complex 1 (mTORC1) pathway under DA depletion and L-DOPA therapy. Sirolimus 136-145 CREB regulated transcription coactivator 1 Mus musculus 157-163 32848709-10 2020 Inhibition of mTORC1 by coadministration of rapamycin to L-DOPA was able to limit the magnitude of LID expression, accounting for a therapeutic effect of this drug. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 14-20 32850834-3 2020 Among the nutrient-sensing pathways, the mechanistic target of rapamycin complex 1 (mTORC1) acts as the central regulator of cellular functions, which include autophagy. Sirolimus 63-72 CREB regulated transcription coactivator 1 Mus musculus 84-90 32502382-1 2020 The TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 142-151 CREB regulated transcription coactivator 1 Mus musculus 163-169 32554565-7 2020 In each case, the insulin-induced phosphorylation was abrogated by mTORC1 inhibitor rapamycin. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 67-73 32764389-1 2020 The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of metabolism that integrates environmental inputs, including nutrients, growth factors, and stress signals. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 32764289-2 2020 Amino acid signaling is mediated via two pathways: the mammalian target of rapamycin complex 1 (mTORC1) and the amino acid responsive (AAR) pathways. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 96-102 32748349-7 2021 Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Sirolimus 185-194 CREB regulated transcription coactivator 1 Mus musculus 205-211 32436749-3 2020 In the current study, we identified that mammalian target of rapamycin complex 1 (mTORC1) activation plays an important role in regulating the detrimental effects of SFA palmitate in hepatocytes, in specific cell death, and TG overproduction. Sirolimus 61-70 CREB regulated transcription coactivator 1 Mus musculus 82-88 32642911-11 2020 Rapamycin could prevent the aggravation of HTG-associated AP via inhibiting mTORC1/S6K1 pathway. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 76-82 32553594-10 2020 In addition, Cyld gene gain- and/or loss-of-function approaches in vitro and in vivo demonstrated that CYLD mediated cardiomyocyte death associated with impaired reactivation of mechanistic target of rapamycin complex 1 (mTORC1) and upregulated Ras genes from rat brain 7 (Rab7), two key components for autolysosomal degradation. Sirolimus 200-209 CREB regulated transcription coactivator 1 Mus musculus 221-227 32470351-7 2020 U50,488H increased alcohol drinking, and pretreatment with rapamycin, at a dose lower than effective doses, blocked the U50,488H-promoted alcohol intake in a dose-dependent manner, indicating a mTORC1-mediated mechanism. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 194-200 32470351-2 2020 Mammalian target of rapamycin complex 1 (mTORC1) pathway in mouse striatum is highly involved in excessive alcohol intake and seeking, and in the U50,488H-induced conditioned place aversion. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 41-47 32470351-4 2020 This study focuses on: (1) how chronic excessive alcohol drinking (4-day drinking-in-the-dark paradigm followed by 3-week chronic intermittent access drinking paradigm [two-bottle choice, 24-h access every other day]) affected nuclear transcript levels of the mTORC1 pathway genes in mouse nucleus accumbens shell (NAcs), using transcriptome-wide RNA sequencing analysis; and (2) whether selective mTORC1 inhibitor rapamycin could alter excessive alcohol drinking and prevent U50,488H-promoted alcohol intake. Sirolimus 415-424 CREB regulated transcription coactivator 1 Mus musculus 260-266 32470351-8 2020 Our results provide supportive and direct evidence relevant to the transcriptional profiling of the critical mTORC1 genes in mouse NAc shell: with functional and pharmacological effects of rapamycin, altered nuclear transcripts in the mTORC1 signaling pathway after excessive alcohol drinking may contribute to increased alcohol intake triggered by KOP-r activation. Sirolimus 189-198 CREB regulated transcription coactivator 1 Mus musculus 109-115 32470351-8 2020 Our results provide supportive and direct evidence relevant to the transcriptional profiling of the critical mTORC1 genes in mouse NAc shell: with functional and pharmacological effects of rapamycin, altered nuclear transcripts in the mTORC1 signaling pathway after excessive alcohol drinking may contribute to increased alcohol intake triggered by KOP-r activation. Sirolimus 189-198 CREB regulated transcription coactivator 1 Mus musculus 235-241 32689970-1 2020 BACKGROUND: To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy (DR), and to find new targets and new methods for the treatment of DR. METHODS: A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 104-110 32505344-2 2020 While 5"-adenosine monophosphate-activated protein kinase (AMPK) is a negative regulator of adipocyte differentiation and lipid accumulation, activation of mammalian target of rapamycin complex 1 (mTORC1), which is inhibited by AMPK, is required for adipocyte differentiation and positively regulates lipid accumulation. Sirolimus 176-185 CREB regulated transcription coactivator 1 Mus musculus 197-203 32722591-5 2020 The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Sirolimus 226-235 CREB regulated transcription coactivator 1 Mus musculus 247-253 32660632-10 2020 Suppression of mTORC1/p70S6K pathway by either rapamycin or p70S6K knockdown promoted heterochromatin organization and ameliorated Dox- or H2O2-induced DNA damage and senescence. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 15-21 32765227-4 2020 Inactivating mutations in TSC genes (TSC1/TSC2) cause sustained Ras homologue enriched in brain (RHEB) activation of the mammalian isoform of the target of rapamycin complex 1 (mTORC1). Sirolimus 156-165 CREB regulated transcription coactivator 1 Mus musculus 177-183 32469097-7 2020 Supplementing miR-196b-5p activity in progenitor cells reduced the protein level of TSC1 and activated mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 144-150 32298692-2 2020 Rapamycin complexes with the immunophilin FKBP12, which subsequently binds and inhibits mTORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 88-94 32615541-6 2020 In contrast, the inhibition of mTORC1 activity by rapamycin suppressed autophagosome degradation but mitigated the cell invasion ability and LM potential of Galphah-overexpressing HCC1806 cells. Sirolimus 50-59 CREB regulated transcription coactivator 1 Mus musculus 31-37 32421368-12 2020 We found that mTORC1 inhibition with low doses of rapamycin (2, 20 nM) lowered macrophage priming of IL-1b mRNA and secretion of IL-1b caused by multiple statins. Sirolimus 50-59 CREB regulated transcription coactivator 1 Mus musculus 14-20 31961063-2 2020 Activation of mechanistic target of rapamycin complex 1 (mTORC1) is regulated by amino acid levels. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 57-63 32475313-7 2020 Significant reductions of renal T lymphocyte and macrophage together with inhibition of cell proliferation were observed in rapamycin treated rats suggesting a role of mTORC1 independent of NOX4 in the proliferation of immune cell. Sirolimus 124-133 CREB regulated transcription coactivator 1 Mus musculus 168-174 32604881-2 2020 This unique organelle plays a critical role in restricting mechanistic target of rapamycin complex 1 (mTORC1) signaling, which is essential for quiescent cells to maintain their quiescence. Sirolimus 81-90 CREB regulated transcription coactivator 1 Mus musculus 102-108 32101625-6 2020 Moreover, NPY activated mTORC1 pathway in articular chondrocytes, while the administration of rapamycin (an mTORC1 inhibitor) in vitro abrogated NPY-mediated effects. Sirolimus 94-103 CREB regulated transcription coactivator 1 Mus musculus 108-114 32612145-8 2020 Finally, we show that inhibition of mTORC1 with rapamycin in ACD mucosal explants reduces p-4EBP and production of IL-15, a master cytokine produced by epithelial cells in this disorder. Sirolimus 48-57 CREB regulated transcription coactivator 1 Mus musculus 36-42 32612825-2 2020 The mechanistic target of rapamycin complex 1 (mTORC1) is a central hub of translation regulation, processing extra- and intra-cellular signals of nutrient availability and physiological state, such as amino acids and energy. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 32612825-6 2020 A third group of mice was fed an adequate protein diet and treated with the mTORC1 inhibitor rapamycin (4 mg/kg every other day) intraperitoneally, with the first two groups treated with vehicle as control. Sirolimus 93-102 CREB regulated transcription coactivator 1 Mus musculus 76-82 32612825-11 2020 Mammary phosphorylation of mTORC1"s downstream targets were decreased by protein restriction and rapamycin treatment (P < 0.05), while very little effect was observed in the liver of rapamycin treated mice, and none by protein restriction. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 27-33 32612825-11 2020 Mammary phosphorylation of mTORC1"s downstream targets were decreased by protein restriction and rapamycin treatment (P < 0.05), while very little effect was observed in the liver of rapamycin treated mice, and none by protein restriction. Sirolimus 183-192 CREB regulated transcription coactivator 1 Mus musculus 27-33 32372406-2 2020 alpha2 -AMPK activity-deficient mice have lower contraction-stimulated protein synthesis Increasing glycogen activates mTORC1-S6K1 independently of AMPK alpha2 Normalizing muscle glycogen content rescues reduced protein synthesis in AMPK-deficient mice ABSTRACT: Objective The mammalian Target of Rapamycin Complex 1 (mTORC1)-S6K1 signalling pathway regulates muscle growth-related protein synthesis and is antagonized by AMP-activated protein kinase (AMPK) in multiple cell types. Sirolimus 297-306 CREB regulated transcription coactivator 1 Mus musculus 119-125 32579942-1 2020 Tuberous sclerosis complex (TSC) is a neurogenetic disorder that leads to elevated mechanistic targeting of rapamycin complex 1 (mTORC1) activity. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 129-135 32655497-6 2020 The insulin-resistant state, commonly reported in AD brain, results in neuronal glucose deprivation, due to a dampening down of the PI3K/Akt pathway, including overactivity of the mammalian target of rapamycin 1 (mTORC1) complex, hyperphosphorylation of p53 and neuronal death. Sirolimus 200-209 CREB regulated transcription coactivator 1 Mus musculus 213-219 32531927-4 2020 We found that the drugs simultaneously disrupt the BRAF V600E-driven extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activity and the mechanistic target of rapamycin complex 1 (mTORC1) signaling in melanoma cells. Sirolimus 192-201 CREB regulated transcription coactivator 1 Mus musculus 213-219 32549199-7 2020 The mTORC1 inhibitor rapamycin abolished the increase in LC3-I and p62. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 32561715-2 2020 The mechanistic target of rapamycin complex 1 (mTORC1) is a well-conserved negative regulator of autophagy. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 32434914-4 2020 Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced AMD-like pathologies. Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 131-137 32516310-1 2020 Unc-51-like autophagy activating kinase 1 (ULK1)-autophagy-related 13 (ATG13) is the most upstream autophagy initiation complex that is phosphorylated by mammalian target-of-rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK) to induce autophagy in asynchronous conditions. Sirolimus 174-183 CREB regulated transcription coactivator 1 Mus musculus 195-201 32312749-1 2020 The mammalian target of rapamycin complex 1 (mTORC1) senses nutrients to mediate anabolic processes within the cell. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 32350925-7 2020 Importantly, these effects were mediated by the mammalian target of rapamycin complex 1 (mTORC1)-RPS6 pathway. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 89-95 32336756-1 2020 BACKGOUND: The mechanistic target of rapamycin complex 1 (mTORC1) is important in the development and progression of many cancers. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 32347294-4 2020 Short-term rapamycin treatment inhibits the kinase activity of mTORC1 but not mTORC2. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 63-69 32278045-0 2020 The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 94-100 32444657-3 2020 However, RE-induced rapamycin-sensitive mechanistic target of rapamycin complex 1 (mTORC1) activation is higher and has a longer duration than after AE. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 83-89 32470053-12 2020 Rapamycin-sensitive insulin treatment and amino acids increased S297 phosphorylation, suggesting that the response to food intake might be regulated via the insulin-mTORC1 pathway. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 165-171 32518628-1 2020 A complex molecular machinery converges on the surface of lysosomes to ensure that the growth-promoting signaling mediated by mechanistic target of rapamycin complex 1 (mTORC1) is tightly controlled by the availability of nutrients and growth factors. Sirolimus 148-157 CREB regulated transcription coactivator 1 Mus musculus 169-175 32280987-8 2020 mTORC1 inhibition with rapamycin significantly improved survival of CKO animals and prevented observed seizures, including for up to forty days following rapamycin withdrawal. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 0-6 32280987-8 2020 mTORC1 inhibition with rapamycin significantly improved survival of CKO animals and prevented observed seizures, including for up to forty days following rapamycin withdrawal. Sirolimus 154-163 CREB regulated transcription coactivator 1 Mus musculus 0-6 31982508-1 2020 Leucine, nutrient signal and substrate for the branched chain aminotransferase (BCAT) activates the mechanistic target of rapamycin (mTORC1) and regulates autophagic flux, mechanisms implicated in the pathogenesis of neurodegenerative conditions such as Alzheimer"s disease (AD). Sirolimus 122-131 CREB regulated transcription coactivator 1 Mus musculus 133-139 32444657-3 2020 However, RE-induced rapamycin-sensitive mechanistic target of rapamycin complex 1 (mTORC1) activation is higher and has a longer duration than after AE. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 83-89 32444657-6 2020 In this study, we used an electrical stimulation-induced RE model in rats, with rapamycin as an inhibitor of mTORC1 activation. Sirolimus 80-89 CREB regulated transcription coactivator 1 Mus musculus 109-115 31917615-8 2020 Rapamycin, an inhibitor of mTORC1, alleviated the hypoxia-induced exacerbation of PAH in DP1-/- mice. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 27-33 32433973-4 2020 We demonstrate that Lunapark interacts with mechanistic target of rapamycin complex-1 (mTORC1), a central cellular regulator that coordinates growth and metabolism with environmental conditions. Sirolimus 66-75 CREB regulated transcription coactivator 1 Mus musculus 87-93 32421369-6 2020 Furthermore, the glucagon-induced upregulation of FGF21 mRNA translation is associated with suppressed activity of the mechanistic target of rapamycin in complex 1 (mTORC1). Sirolimus 141-150 CREB regulated transcription coactivator 1 Mus musculus 165-171 32421369-7 2020 Similarly, the results show that rapamycin-induced suppression of mTORC1 leads to upregulation of FGF21 mRNA translation with no change in FGF21 mRNA abundance. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 66-72 32375878-2 2020 TSC1 and TSC2 are repressors of the mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 79-85 32375878-13 2020 Chronic, but not acute treatment, with the mTORC1 inhibitor rapamycin reversed the impairment in synaptic inhibition. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 43-49 31958214-9 2020 We conclude that loss of TSC1 or TSC2 led to upregulated expression of PFKFB3 through activation of mTORC1/HIF-1alpha signaling pathway and co-administration of rapamycin and PFK15 may be a promising strategy for the treatment of TSC tumors as well as other hyperactivated mTORC1-related tumors. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 273-279 32062191-9 2020 The results indicate that rapamycin inhibits BAFF-stimulated B-cell proliferation and survival by blunting mTORC1/2-mediated [Ca2+]i elevations and suppressing Ca2+-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 107-113 31958214-2 2020 The main etiology of TSC is the loss-of-function mutation of TSC1 or TSC2 gene, which leads to aberrant activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 159-165 32092760-0 2020 Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 60-66 31965176-1 2020 Mechanistic target of rapamycin complex 1 (mTORC1) is a highly evolutionarily conserved serine/threonine kinase that regulates cell growth and metabolism in response to multiple environmental cues, such as nutrients, hormones, energy, and stress. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 31875479-1 2020 BACKGROUND: The protein kinase target of rapamycin (mTOR) in complex 1 (mTORC1) is activated by amino acids and in turn upregulates anabolic processes. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 72-78 32092760-2 2020 To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Sirolimus 65-74 CREB regulated transcription coactivator 1 Mus musculus 79-85 32311329-1 2020 Using cryo-electron microscopy and molecular characterization, David Sabatini and colleagues provide crucial new insights that validate and expand their model of how amino acids are sensed and signal at the lysosome to activate mechanistic target of rapamycin complex 1 (mTORC1) and cell growth-regulating processes. Sirolimus 250-259 CREB regulated transcription coactivator 1 Mus musculus 271-277 32275833-5 2020 Meanwhile, the myogenic regulatory factors (MRFs) and the mammalian target of rapamycin complex 1 (mTORC1) pathway showed the same tendencies of changes as the differentiation of SCs. Sirolimus 78-87 CREB regulated transcription coactivator 1 Mus musculus 99-105 32275833-6 2020 After Lys was resupplemented with rapamycin, the mTORC1 pathway was inhibited, and the differentiation ability of SCs was suppressed. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 49-55 31898848-5 2020 NPRL3 is a component of the GAP Activity Towards Rags 1 (GATOR1) protein complex that inhibits mammalian Target of Rapamycin Complex 1 (mTORC1) activity and it is found mutated in familial focal cortical dysplasia and familial focal epilepsy. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 136-142 32287270-4 2020 The best-known function of SESN2 is the inhibition of the mechanistic target of rapamycin complex 1 kinase (mTORC1) that plays a central role in support of cell growth and suppression of autophagy. Sirolimus 80-89 CREB regulated transcription coactivator 1 Mus musculus 108-114 31876121-3 2020 They demonstrated that CD4+ T cells isolated from Takayasu"s arteritis (TAK) are biased to differentiate into Th1 and Th17 cells because of mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 183-189 31876121-4 2020 Subsequently, using human artery-NSG chimera model, they showed that mTORC1 inhibition, by either rapamycin or RNAi technology, effectively abrogated the mal-differentiation of TAK CD4+ T cells and vascular inflammation. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 69-75 32348753-1 2020 Mechanistic target of rapamycin complex 1 (mTORC1) is a master modulator of cellular growth, and its aberrant regulation is recurrently documented within breast cancer. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 32035621-3 2020 Unlike other autophagy genes, KO of ULK1 or ATG13 attenuated ER stress and promoted mammalian target of rapamycin complex 1 (mTORC1) activation. Sirolimus 104-113 CREB regulated transcription coactivator 1 Mus musculus 125-131 32068977-7 2020 In terms of mechanism, we found mTORC1 activity was impaired by downregulation of METTL3, additional silencing of METTL3 cannot further decrease the phosphorylation level of mTORC1 and glycolysis activity in Rapamycin-treated HCC cells. Sirolimus 208-217 CREB regulated transcription coactivator 1 Mus musculus 174-180 32235551-6 2020 The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 33-39 32279295-3 2020 The FLCN protein functions in multiple signaling and metabolic pathways including positive regulation of mechanistic target of rapamycin complex 1 (mTORC1) activity via FLCN"s GTPase (GAP) activity for Rag C, positive regulation of Wnt signaling (in mesenchymal cells), and negative regulation of TFE3 nuclear localization. Sirolimus 127-136 CREB regulated transcription coactivator 1 Mus musculus 148-154 32188096-1 2020 Ras homolog protein enriched in brain (Rheb) is a key activator of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 108-114 31930970-5 2020 In addition, LPS stimulation potently induced transcriptional upregulation of RagD, an important activation factor of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 159-165 31786107-11 2020 Inhibition of mTORC1 by rapamycin or siRNA can lead to dissociation of alphaB-crystallin from the ATP6V1A and mTORC1complex, shortening the half-life of ATP6V1A and increasing the lysosomal pH. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 31904289-7 2020 Mechanistically, UNX-induced mammalian target of rapamycin complex 1 (mTORC1) signaling to phosphorylation of ribosomal protein S6 (rpS6) in the remaining kidney is markedly inhibited in Pik3c3-hypomorphic mice. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 70-76 31623699-1 2020 The present study was conducted to evaluate the effects of glucose, soya oil or glutamine on jejunal morphology, protein metabolism and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway in jejunal villus or crypt compartment of piglets. Sirolimus 182-191 CREB regulated transcription coactivator 1 Mus musculus 203-209 32127537-5 2020 Treatment of G2-Terc-/- mice with rapamycin, an inhibitor of mTORC1, decreases survival, in contrast to lifespan extension in wild-type controls. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 61-67 31786107-11 2020 Inhibition of mTORC1 by rapamycin or siRNA can lead to dissociation of alphaB-crystallin from the ATP6V1A and mTORC1complex, shortening the half-life of ATP6V1A and increasing the lysosomal pH. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 110-116 32058469-3 2020 PURPOSE: We investigated the effect of cancer cachexia on the diurnal regulation of feeding, physical activity, and skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) signaling in tumor-bearing mice. Sirolimus 154-163 CREB regulated transcription coactivator 1 Mus musculus 175-181 31651100-2 2020 It is well established that Mammalian Target of Rapamycin Complex 1 (mTORC1) signalling is a key modulator in mediating increases in skeletal muscle mass and function. Sirolimus 48-57 CREB regulated transcription coactivator 1 Mus musculus 69-75 31891737-4 2020 DGKbeta induced neurite outgrowth by activation of mammalian target of rapamycin complex 1 (mTORC1) through a kinase-dependent pathway. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 92-98 31769520-9 2020 Although AZD2014 was more effective for cell growth inhibition and PDT enhancement than rapamycin at the higher concentrations examined in the study, both inhibitors effectively enhanced PDT response, suggesting that inhibition of mTORC1 is crucial for PDT enhancement. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 231-237 31823466-3 2020 Previous work from our laboratory indicated that short-term (10-week) treatment with rapamycin, an mTORC1 inhibitor, improved measures of these age-related changes. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 99-105 30972602-3 2020 The mammalian target of rapamycin complex 1 (mTORC1) is upregulated by UVB. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 31794259-2 2020 Grb10 is also a substrate for the mechanistic target of rapamycin complex 1 (mTORC1) that mediates its feedback inhibition on phosphatidylinositide 3-kinase (PI3K)/Akt signaling. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 77-83 31794259-7 2020 However, acute inhibition of mTORC1 with rapamycin blocked Grb10 Ser476 phosphorylation and repressed a negative-feedback loop on PI3K/Akt signaling that increased myotube responsiveness to insulin. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 29-35 31886628-1 2020 Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 41-47 31886628-10 2020 Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 104-110 31697050-2 2020 Signalling via the mammalian target of rapamycin complex 1 (mTORC1) regulates proteostasis in skeletal muscle by affecting protein synthesis and autophagosomal protein degradation. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 60-66 31697050-4 2020 However, systemic dampening of mTORC1 signalling by its allosteric inhibitor rapamycin is beneficial at the organismal level and increases lifespan. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 31-37 33406024-4 2020 Methods: Ovalbumin (OVA) T cell receptor transgenic DO11.10 mice (DO11.10 mice) were used to establish NEA model, and few mice received specific mTORC1 inhibitor rapamycin (RAPA) before intranasal administration of OVA. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 145-151 32103032-8 2020 The mTORC1 inhibitor rapamycin also reduced IL-6 and IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 32103032-8 2020 The mTORC1 inhibitor rapamycin also reduced IL-6 and IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 153-159 32023468-1 2020 Mechanistic or mammalian target of rapamycin complex 1 (mTORC1) is an important regulator of effector functions, proliferation, and cellular metabolism in macrophages. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 56-62 31903726-4 2020 The ITP found rapamycin, an inhibitor to the pro-growth mTORC1 (mechanistic target of rapamycin complex 1) pathway, improved survival and it suppressed tumors in Apc+/Min mice providing a plausible rationale to ask if acarbose had a similar effect. Sirolimus 14-23 CREB regulated transcription coactivator 1 Mus musculus 56-62 31958467-7 2020 The activation of mammalian target of rapamycin complex-1 (mTORC1) during increased workload in presence of glucose as the only substrate was prevented by C/EBPbeta knockdown, thereby abating contractile dysfunction in cardiomyocytes. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 59-65 31782083-3 2020 We provide evidence that eIF4E phosphorylation is regulated by mTORC1 by virtue of its interaction with Raptor through a novel TPTPNPP motif and consequent phosphorylation invitro and in vivo in a Rapamycin-sensitive manner. Sirolimus 197-206 CREB regulated transcription coactivator 1 Mus musculus 63-69 32015438-1 2020 The Hippo and mammalian target of rapamycin complex 1 (mTORC1) pathways are the two predominant growth-control pathways that dictate proper organ development. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 55-61 31894839-7 2020 Furthermore, EPS1-1-mediated apoptosis is regulated by inactivation of mammalian target of rapamycin complex 1 (mTORC1) and activation of the jun-NH2 kinase (JNK)-p53 signaling axis dependent on AMPK activation. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 112-118 31822355-3 2020 This basic leucine-zipper (bZIP) transcription factor is controlled by the lifespan regulator mechanistic/mammalian target of rapamycin complex 1 (mTORC1) and plays an important role in energy homeostasis and adipose tissue differentiation. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 147-153 31969673-1 2020 The group II metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist LY341495 produces antidepressant-like effects by acting on mammalian target of rapamycin complex 1 (mTORC1) signaling and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in rodent. Sirolimus 149-158 CREB regulated transcription coactivator 1 Mus musculus 170-176 31969673-8 2020 These effects were blocked by pretreatment with the AMPA receptor inhibitor 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo(f)quinoxaline (NBQX) and the mTORC1 inhibitor rapamycin. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 144-150 31973180-5 2020 Moreover, the molecular relevance of endothelial nitric oxide synthase (eNOS) and mechanistic/mammalian target of rapamycin complex 1 (mTORC1) was studied in both cardiac tissue and HL-1 cardiomyocytes. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 135-141 31669651-1 2020 Mechanistic target of rapamycin complex 1 (mTORC1) plays crucial roles in male fertility. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 31959796-8 2020 The Pdgfb induction system was distinct from that of inflammatory cytokines mediated by mechanistic target of rapamycin complex 1 (mTORC1) and NFkappaB signaling. Sirolimus 110-119 CREB regulated transcription coactivator 1 Mus musculus 131-137 31963899-6 2020 Leucine, a BCAA, and its metabolite, beta-hydroxy-beta-methylbutyrate (HMB), both activate mammalian target of rapamycin complex 1 (mTORC1) and increase protein synthesis, but the mechanisms of activation appear to be different. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 132-138 31669651-4 2020 In the present study, it was found that treatment of rapamycin, an mTORC1 inhibitor, resulted in infertility with decreased milt production and sperm motility in zebrafish. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 67-73 31834371-1 2020 Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 209-215 31924779-4 2020 Mechanistically, macropinocytosis in T cells provides access of extracellular AA to an endolysosomal compartment to sustain activation of the mechanistic target of rapamycin complex 1 (mTORC1) that promotes T cell growth. Sirolimus 164-173 CREB regulated transcription coactivator 1 Mus musculus 185-191 32553647-9 2020 The activation of mammalian target of rapamycin complex 1 (mTORC1), a central regulator of autophagy, was found to be negatively correlated with autophagic synthesis; moreover, pharmacological inhibition of mTORC1 by rapamycin alleviated hepatic steatosis through recovery of autophagic flux in hepatocytes with prolonged PA treatment. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 59-65 32553647-9 2020 The activation of mammalian target of rapamycin complex 1 (mTORC1), a central regulator of autophagy, was found to be negatively correlated with autophagic synthesis; moreover, pharmacological inhibition of mTORC1 by rapamycin alleviated hepatic steatosis through recovery of autophagic flux in hepatocytes with prolonged PA treatment. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 207-213 32553647-9 2020 The activation of mammalian target of rapamycin complex 1 (mTORC1), a central regulator of autophagy, was found to be negatively correlated with autophagic synthesis; moreover, pharmacological inhibition of mTORC1 by rapamycin alleviated hepatic steatosis through recovery of autophagic flux in hepatocytes with prolonged PA treatment. Sirolimus 217-226 CREB regulated transcription coactivator 1 Mus musculus 59-65 32553647-9 2020 The activation of mammalian target of rapamycin complex 1 (mTORC1), a central regulator of autophagy, was found to be negatively correlated with autophagic synthesis; moreover, pharmacological inhibition of mTORC1 by rapamycin alleviated hepatic steatosis through recovery of autophagic flux in hepatocytes with prolonged PA treatment. Sirolimus 217-226 CREB regulated transcription coactivator 1 Mus musculus 207-213 31921404-2 2020 The aberrant activation of mTORC1 in TSC has led to treatment with mTORC1 inhibitor rapamycin as a lifelong therapy for tumors, but TSC-associated neurocognitive manifestations remain unaffected by rapamycin. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 27-33 31921404-2 2020 The aberrant activation of mTORC1 in TSC has led to treatment with mTORC1 inhibitor rapamycin as a lifelong therapy for tumors, but TSC-associated neurocognitive manifestations remain unaffected by rapamycin. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 67-73 33834178-10 2020 Immunohistochemistry assays of rpS6 phosphorylation showed that rapamycin reduction of mTORC1 activity was on the same level, with the most prominent difference being in intestinal crypt Paneth cells in both sexes. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 87-93 33834178-13 2020 Conclusions: In males and females, these findings link rapamycin-mediated intestinal polyposis prevention with mTORC1 inhibition in Paneth cells and concomitant reduced epithelial cell proliferation. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 111-117 31819177-8 2020 siRNA knockdown of Raptor or treatment with rapamycin inhibited PKD1-accelerated lactate production as well as glucose consumption in cells, which confirms the association of mTORC1 with PKD1-induced metabolic alterations. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 175-181 32356448-6 2020 Increased apoptotic cells were observed in mTORC1 inhibition by Rapamycin administration. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 43-49 32641600-1 2020 Mechanistic target of rapamycin complex 1 (mTORC1) plays a pivotal role in controlling cell growth and metabolism in response to nutrients and growth factors. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 43-49 32502530-5 2020 IGF-1 signaling or its downstream effector mTORC1 were inhibited by administering BMS-754807 or rapamycin, respectively. Sirolimus 96-105 CREB regulated transcription coactivator 1 Mus musculus 43-49 32502530-11 2020 Similarly, rapamycin inhibition of mTORC1 during the growth factor surge blunted the regenerative response. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 35-41 33183203-4 2020 An innovative strategy involves the vitamin nicotinamide and the pathways associated with the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and clock genes. Sirolimus 210-219 CREB regulated transcription coactivator 1 Mus musculus 244-250 32579497-3 2020 Alcohol via upstream kinases like mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCepsilon or vice versa in AUD. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 75-81 31241126-4 2020 Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Sirolimus 6-15 CREB regulated transcription coactivator 1 Mus musculus 75-81 31241126-4 2020 Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Sirolimus 17-20 CREB regulated transcription coactivator 1 Mus musculus 75-81 31241126-4 2020 Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 75-81 31241126-4 2020 Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Sirolimus 148-151 CREB regulated transcription coactivator 1 Mus musculus 75-81 31625572-3 2020 Phosphoinositide 3-kinase (PI3K)/AKT signaling activates mammalian target of rapamycin complex 1 (mTORC1) and hyperactivation of mTORC1 is a common event in PKD; however, mTORC1 inhibitors have yielded disappointing results in clinical trials. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 98-104 32395334-7 2020 mTORC1 signaling was inhibited using rapamycin. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 0-6 31746373-15 2020 Furthermore, rapamycin prevented angiotensin II-induced H9c2 cell apoptosis and promoted autophagy by inhibiting the mTORC1 and ER stress pathways. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 117-123 31949495-1 2020 Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) plays a critical role in tumorigenesis. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 68-74 30794726-1 2020 Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and humans. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 14-20 30794726-1 2020 Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and humans. Sirolimus 89-98 CREB regulated transcription coactivator 1 Mus musculus 14-20 30794726-1 2020 Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and humans. Sirolimus 206-215 CREB regulated transcription coactivator 1 Mus musculus 14-20 30794726-4 2020 Instead, modestly but specifically inhibiting mTORC1 via a variety of emerging techniques, including intermittent or transient treatment with rapamycin derivatives, or specific dietary regimens, may be sufficient to promote health and longevity with reduced side effects. Sirolimus 142-151 CREB regulated transcription coactivator 1 Mus musculus 46-52 32821719-4 2020 The mammalian target of rapamycin complex 1 (mTORC1) pathway plays a key role in sensing cellular nutrient and energy status and regulating the proliferation and growth of cells by controlling various anabolic and catabolic processes. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 31701625-1 2020 The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 176-185 CREB regulated transcription coactivator 1 Mus musculus 197-203 32921582-1 2020 The giant 532 kDa HERC1 protein is a ubiquitin ligase that interacts with tuberous sclerosis complex subunit 2 (TSC2), a negative upstream regulator of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 176-185 CREB regulated transcription coactivator 1 Mus musculus 197-203 32579497-5 2020 Mammalian target to rapamycin complex 1 (mTORC1), another form of mTOR complex regulates translation of synaptic proteins involved in alcohol-induced plasticity. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 41-47 31841452-6 2020 Further experiments showed that alpha-KG down-regulated the expression of M1-polarized marker genes and inhibited the activities of mammalian target of rapamycin complex 1 (mTORC1)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway in M1-polarized MH-S cells. Sirolimus 152-161 CREB regulated transcription coactivator 1 Mus musculus 173-179 31921198-7 2019 After infected by Micrococcus luteus or Listonella anguillarum, mRNA expression of Ss-Raptor rapidly increased within 48 h. Once Raptor/mTORC1 signaling was blocked by rapamycin, expression of the pro-inflammatory cytokines IL-1beta and IL-8 was severely impaired, suggesting potential regulatory role of Raptor/mTORC1 signaling in the innate immune response of rockfish. Sirolimus 168-177 CREB regulated transcription coactivator 1 Mus musculus 136-142 31878201-2 2019 Sirolimus (rapamycin), an allosteric mTORC1 inhibitor, is a therapeutic option for women with LAM but it only maintains lung volume during treatment and does not provide benefit for all LAM patients. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 37-43 31878201-2 2019 Sirolimus (rapamycin), an allosteric mTORC1 inhibitor, is a therapeutic option for women with LAM but it only maintains lung volume during treatment and does not provide benefit for all LAM patients. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 37-43 31444991-8 2020 Importantly, both accelerated wound healing and fibrotic phenotypes were largely reversed by the mTORC1 inhibitor, rapamycin. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 97-103 31882658-6 2019 Inhibition of mTORC1 with Rapamycin elicited reciprocal activation of mTORC2, enhanced autophagy and recruited anti-apoptotic signals, conferring protection from calcification. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 14-20 31493485-8 2019 This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 56-62 31493485-8 2019 This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 141-147 31493485-9 2019 Based on our results, even when mTORC2 is less stable compared with mTORC1, it can be less inhibited by rapamycin. Sirolimus 104-113 CREB regulated transcription coactivator 1 Mus musculus 68-74 31857853-2 2019 Many of the effects of SESTRINs are mediated by negative and positive regulation of mechanistic target of rapamycin kinase complexes 1 and 2 (mTORC1 and mTORC2), respectively, that are often deregulated in human cancers where they support cell growth, proliferation, and cell viability. Sirolimus 106-115 CREB regulated transcription coactivator 1 Mus musculus 142-148 31921637-4 2019 The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of numerous cellular processes implicated in proliferation, metabolism, and cell growth. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 57-63 31820733-1 2019 The mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in dendritic translation and in learning and memory. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 31921849-2 2019 Here we show that both global mRNA translation and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) kinase activity are declined in a senescent model of mouse embryonic fibroblasts (MEFs). Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 104-110 31813279-5 2019 Furthermore, both loss and gain-of-function assays strengthen the evidence that MELK enforces the malignant phenotype of ccRCC cells through over-activating the mammalian target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 181-190 CREB regulated transcription coactivator 1 Mus musculus 202-208 31676287-3 2019 Under the control of mammalian target of rapamycin complex 1 (mTORC1), LARP1 regulates translation of these transcripts. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 62-68 31487268-8 2019 The mTOR complex (mTORC)1 inhibitor rapamycin suppressed proinflammatory cytokine production by T cells and alleviated autoimmunity in Srsf1-deficient mice. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 18-25 31461340-5 2019 This review summarizes the current knowledge of the mechanisms that underpin MPS, which are broadly divided into mechanistic target of rapamycin complex 1 (mTORC1)-dependent, mTORC1-independent, and ribosomal biogenesis-related, and describes the evidence that shows how they are regulated by anabolic stimuli (exercise and/or nutrition) in healthy human skeletal muscle. Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 156-162 31299246-2 2019 Rapamycin (sirolimus) treatment suppresses mTORC1 but also induces autophagy, which promotes the survival of TSC2-deficient cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 43-49 31299246-2 2019 Rapamycin (sirolimus) treatment suppresses mTORC1 but also induces autophagy, which promotes the survival of TSC2-deficient cells. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 43-49 31299246-3 2019 Based on the hypothesis that simultaneous inhibition of mTORC1 and autophagy would limit the availability of critical nutrients and inhibit LAM cells, we conducted a phase 1 clinical trial of sirolimus and hydroxychloroquine for LAM. Sirolimus 192-201 CREB regulated transcription coactivator 1 Mus musculus 56-62 31599935-4 2019 These effects were regulated by hyperactivation of mammalian target of rapamycin complex 1(mTORC1) signaling, and thereby inhibition of autophagy and induction of ER stress in growth plate chondrocytes. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 91-97 31599935-5 2019 Intraperitoneal injection of mTORC1 inhibitor, rapamycin, to mice with Sirt1 deletion, partially neutralized such inhibitory effects of Sirt1 ablation on longitudinal bone growth, indicating the causative link between SIRT1 and mTORC1 signaling in the growth plate. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 29-35 31599935-5 2019 Intraperitoneal injection of mTORC1 inhibitor, rapamycin, to mice with Sirt1 deletion, partially neutralized such inhibitory effects of Sirt1 ablation on longitudinal bone growth, indicating the causative link between SIRT1 and mTORC1 signaling in the growth plate. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 228-234 31659101-1 2019 BACKGROUND: Hyperactivity of the mechanistic target of rapamycin complex 1 (mTORC1) is implicated in a variety of diseases such as cancer and diabetes. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 76-82 31650481-1 2019 Inhibition of mammalian target of rapamycin complex I (mTORC1) by rapamycin improves cardiac function in both aging and heart failure. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 55-61 31650481-1 2019 Inhibition of mammalian target of rapamycin complex I (mTORC1) by rapamycin improves cardiac function in both aging and heart failure. Sirolimus 66-75 CREB regulated transcription coactivator 1 Mus musculus 55-61 31676673-2 2019 In response to low energy, AMPK stimulates catabolic pathways such as autophagy to enhance energy production while inhibiting anabolic pathways regulated by the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 183-192 CREB regulated transcription coactivator 1 Mus musculus 204-210 31801253-4 2019 In this study, we investigated whether SCs participate directly in Lys-induced skeletal muscle growth and whether the mammalian target of rapamycin complex 1 (mTORC1) pathway was activated both in vivo and in vitro to mediate SC functions in response to Lys supplementation. Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 159-165 31801253-8 2019 After verifying that rapamycin inhibits the mTORC1 pathway and suppresses SC proliferation, we conclude that Lys is not only a molecular building block for protein synthesis but also a signal that activates SCs to manipulate muscle growth via the mTORC1 pathway. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 44-50 31801253-8 2019 After verifying that rapamycin inhibits the mTORC1 pathway and suppresses SC proliferation, we conclude that Lys is not only a molecular building block for protein synthesis but also a signal that activates SCs to manipulate muscle growth via the mTORC1 pathway. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 247-253 31554636-7 2019 Additionally, the HRI-eIF2alphaP-ATF4 pathway represses mechanistic target of rapamycin complex 1 (mTORC1) signaling, specifically in the erythroid lineage as a feedback mechanism of erythropoietin-stimulated erythropoiesis during iron/heme deficiency. Sirolimus 78-87 CREB regulated transcription coactivator 1 Mus musculus 99-105 31693882-2 2019 The kinase mechanistic target of rapamycin (mTOR) forms the enzymatic core of the highly conserved mTOR complexes mTORC1 and mTORC2. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 114-120 30890204-6 2019 Interestingly, Ad-Cyp8b1 increased ceramide synthesis and activated hepatic mechanistic target of rapamycin complex 1 (mTORC1)-p70S6K signaling cascade and inhibited AKT/insulin signaling in mice. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 119-125 31136010-5 2019 Using a zebrafish liver extreme injury model, we found that mammalian target of rapamycin complex 1 (mTORC1) signaling regulated dedifferentiation of BECs and proliferation of BP-PCs. Sirolimus 80-89 CREB regulated transcription coactivator 1 Mus musculus 101-107 31678320-2 2019 Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a mega protein complex that promotes energy-consuming anabolic processes of protein and nucleic acid synthesis as well lipogenesis in times of energy and nutrient abundance. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 53-59 31740775-3 2019 Asparagine limitation in melanoma and pancreatic cancer cells activates receptor tyrosine kinase-MAPK signalling as part of a feedforward mechanism involving mammalian target of rapamycin complex 1 (mTORC1)-dependent increase in MAPK-interacting kinase 1 (MNK1) and eukaryotic translation initiation factor 4E (eIF4E), resulting in enhanced translation of activating transcription factor 4 (ATF4) mRNA. Sirolimus 178-187 CREB regulated transcription coactivator 1 Mus musculus 199-205 31454827-8 2019 D-methadone increased phospho-p70S6 kinase, a downstream target of mTORC1 in the mPFC, and intra-mPFC infusion of the selective mTORC1 inhibitor rapamycin blocked the antidepressant actions of d-methadone in the FUST and NSFT. Sirolimus 145-154 CREB regulated transcription coactivator 1 Mus musculus 67-73 31454827-8 2019 D-methadone increased phospho-p70S6 kinase, a downstream target of mTORC1 in the mPFC, and intra-mPFC infusion of the selective mTORC1 inhibitor rapamycin blocked the antidepressant actions of d-methadone in the FUST and NSFT. Sirolimus 145-154 CREB regulated transcription coactivator 1 Mus musculus 128-134 31622525-4 2019 We examine how metabolic sensors such as AMP-activated protein kinase (AMPK), mechanistic target of rapamycin complex 1 (mTORC1) and hypoxia inducible factor 1 (HIF1) determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 121-127 31582215-2 2019 Attenuation of mechanistic target of rapamycin complex 1 (mTORC1) activation by repetitive resistance exercise is involved in this process, but the mechanism leading to inactivation of mTORC1 remains unclear. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 31772273-1 2019 Inactivation of the protein complex "mechanistic target of rapamycin complex 1" (mTORC1) can increase the nuclear content of transcriptional regulators of metabolism and apoptosis. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 81-87 31772273-4 2019 In this study, we demonstrate that PKCdelta, a STAT1 kinase, contains a functional "target of rapamycin signaling" (TOS) motif that directs its interaction with mTORC1. Sirolimus 94-103 CREB regulated transcription coactivator 1 Mus musculus 161-167 31772273-5 2019 Depletion of KPNA1 by RNAi prevented the nuclear import of PKCdelta in cells exposed to the mTORC1 inhibitor rapamycin or amino acid restriction. Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 92-98 31672913-1 2019 The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) Activating Protein (GAP) activity toward the GTPase RagC. Sirolimus 106-115 CREB regulated transcription coactivator 1 Mus musculus 127-133 31803749-6 2019 The mTORC1 inhibitor rapamycin prevented the glycine-stimulated protection of myotube diameter, and glycine-stimulated S6 phosphorylation, suggesting that mTORC1 signaling may be necessary for glycine"s protective effects in vitro. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 31803749-6 2019 The mTORC1 inhibitor rapamycin prevented the glycine-stimulated protection of myotube diameter, and glycine-stimulated S6 phosphorylation, suggesting that mTORC1 signaling may be necessary for glycine"s protective effects in vitro. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 155-161 31699965-6 2019 Duman"s group demonstrated that the activation of mammalian target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex is reportedly involved in the antidepressant effects of ketamine. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 91-97 31487224-7 2019 The reduction of protein synthesis was associated with a marked inhibition of mammalian target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, a mechanism consistent with reduced translation initiation. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 119-125 31651917-9 2019 Furthermore, western blot analysis showed that LR1 activated the mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway by increasing the phosphorylation of S6 and 70S6K1 in the gut-liver axis of weaned pigs. Sirolimus 89-98 CREB regulated transcription coactivator 1 Mus musculus 110-116 31673045-6 2019 The present study demonstrates that despite reduced lipogenesis, liver specific SCD1 deficiency activates the mechanistic target of rapamycin complex 1 (mTORC1) along with induction of PGC-1alpha and ER stress. Sirolimus 132-141 CREB regulated transcription coactivator 1 Mus musculus 153-159 31691510-1 2019 Resistance exercise (RE) activates the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway and increases muscle protein synthesis. Sirolimus 61-70 CREB regulated transcription coactivator 1 Mus musculus 82-88 31627299-3 2019 We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2. Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 190-196 31641080-3 2019 In follicular B cells, the expression of genes involved in ribosome biogenesis, aerobic respiration, and mammalian target of rapamycin complex 1 (mTORC1) signaling was reduced when compared to that in transitional B cells. Sirolimus 125-134 CREB regulated transcription coactivator 1 Mus musculus 146-152 31518555-4 2019 For experiment 2, rats were treated with mTORC1 inhibitor rapamycin during 24-h HS. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 41-47 31636571-2 2019 Moreover, the mammalian target of rapamycin complex 1 (mTORC1) is a key signaling complex regulating exercise/nutrient-induced alterations in muscle protein synthesis. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 55-61 31548394-2 2019 Their regulation of tumor growth is closely tied to the ability of these enzymes to mainly stimulate protein synthesis by activating mTORC1 (mammalian target of rapamycin complex 1) signaling, although the exact mechanism is not completely understood. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 133-139 31582588-3 2019 We found that inhibition of the mTORC1-Sch9 pathway by SCH9 deletion, rapamycin or myriocin treatment resulted in a dramatic decrease in H2S production. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 32-38 31582588-7 2019 Finally, we also observed a reduction in H2S production and lowering of both mRNA and protein levels of CGL and CBS in cultured human cells treated with rapamycin to reduce mTORC1 pathway activity. Sirolimus 153-162 CREB regulated transcription coactivator 1 Mus musculus 173-179 31316183-4 2019 We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). Sirolimus 116-125 CREB regulated transcription coactivator 1 Mus musculus 99-105 31373126-2 2019 mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 40-46 31328833-11 2019 Further, T2DM significantly reduced mechanistic target of rapamycin complex 1 (mTORC1) activity (phosphorylation of p70S6KThr389 and 4E-BP1Thr37/46 ) to insulin stimulation and the number of myonuclei in the untrained basal condition, but RT-mediated adaptations were not affected by T2DM. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 79-85 31159662-2 2019 Here, we aimed to establish a new in vitro muscle contraction model for analyzing the activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 141-147 31345937-2 2019 We generated Ngn3RapKO mice (ablation of Raptor, an essential component of mechanistic target of rapamycin [mTORC1] in Ngn3+ endocrine progenitor cells) and found that mTORC1 was dispensable for endocrine cell lineage formation but specifically regulated both proliferation and identity maintenance of neonatal beta-cells. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 108-114 31345937-2 2019 We generated Ngn3RapKO mice (ablation of Raptor, an essential component of mechanistic target of rapamycin [mTORC1] in Ngn3+ endocrine progenitor cells) and found that mTORC1 was dispensable for endocrine cell lineage formation but specifically regulated both proliferation and identity maintenance of neonatal beta-cells. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 168-174 31226256-7 2019 Intracerebroventricular injection of the mTORC1 inhibitor, rapamycin, revealed a role for mTOR in the socially-induced hypertrophy of GnRH1 neurons. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 41-47 31226256-8 2019 Rapamycin treatment also had effects at the pituitary and testes, suggesting involvement of the mTORC1 complex at multiple levels of the reproductive axis. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 96-102 31236744-8 2019 Meanwhile, rapamycin, a specific inhibitor of mTORC1, was co-applied with gentamicin to verify the role of mTOR signaling. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 46-52 31219657-6 2019 Cellular metabolic state is monitored by sensing lysosomal metabolites by the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 119-125 31552299-1 2019 The pathophysiological role of mammalian target of rapamycin complex 1 (mTORC1) in neurodegenerative diseases is established, but possible therapeutic targets responsible for its activation in neurons must be explored. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 72-78 31492813-0 2019 Regulation of GSK3 cellular location by FRAT modulates mTORC1-dependent cell growth and sensitivity to rapamycin. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 55-61 31231029-3 2019 Rapamycin and its analogs target mTORC1 directly; however, chronic treatment in certain cell types and in vivo results in the inhibition of both mTORC1 and mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 33-39 31231029-3 2019 Rapamycin and its analogs target mTORC1 directly; however, chronic treatment in certain cell types and in vivo results in the inhibition of both mTORC1 and mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 145-151 31331823-5 2019 The treatment of denervated animals with rapamycin blocked the stimulatory effects of CGRP on mTORC1 and its inhibitory actions on autophagic flux and NMJ degeneration. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 94-100 30022576-6 2019 We further report that the selective mTORC1 inhibitor, rapamycin, abolishes reinstatement of alcohol place preference. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 37-43 31510109-3 2019 In GBs, mTORC1 inhibitors such as rapamycin have performed poorly in clinical trials, and in vitro protect GB cells from nutrient and oxygen deprivation. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 8-14 31645839-8 2019 Consistently with its known molecular mechanism of action, rapamycin reduced the extent of activation of the so-called "mechanistic" target of rapamycin complex 1 (mTORC1) kinase and the total amount of intracellular proteins. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 164-170 31645839-8 2019 Consistently with its known molecular mechanism of action, rapamycin reduced the extent of activation of the so-called "mechanistic" target of rapamycin complex 1 (mTORC1) kinase and the total amount of intracellular proteins. Sirolimus 143-152 CREB regulated transcription coactivator 1 Mus musculus 164-170 31645839-11 2019 All together these data suggest that the inhibition of mTORC1 in human microglia by rapamycin results in complex immunomodulatory effects, including a significant increase in the expression and release of the pro-inflammatory IL-6. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 55-61 31078684-6 2019 Loss of either Tsc1 or Tsc2 from astrocytes resulted in a marked increase in Aqp4 expression which was sensitive to mTORC1 inhibition with rapamycin. Sirolimus 139-148 CREB regulated transcription coactivator 1 Mus musculus 116-122 31174205-10 2019 Rapamycin failed to rescue GATOR1 protein levels but rather rescued downstream mTORC1 hyperactivity as measured by phosphorylation of S6. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 79-85 31120172-4 2019 We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). Sirolimus 261-270 CREB regulated transcription coactivator 1 Mus musculus 105-111 31201822-5 2019 We demonstrated that HA-19 led to the increase of the protein synthesis by activating mechanistic target of rapamycin complex 1 (mTORC1)/p70 S6K pathways, and also enhanced myoblast proliferation and terminal differentiation via up-regulating of the myogenic transcription factors Pax7, MyoD and Myogenin. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 129-135 31227218-8 2019 In contrast, the mTORC1 inhibitor rapamycin did not have a significant effect on eEF2 dephosphorylation. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 17-23 31434755-4 2019 Systemic treatment with the mTORC1 inhibitor rapamycin reduces alpha-globin precipitates and lessens pathologies in beta-thalassemic mice via an ULK1-dependent pathway. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 28-34 31142473-9 2019 In addition, the mammalian target of rapamycin complex 1 (mTORC1) pathway was remarkably activated in lupus AtMs, and blocking mTORC1 signalling by rapamycin abolished the generation of T-bet+ B cells and terminal differentiation of lupus AtMs. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 31226250-3 2019 On the other hand, eEF-2K is inactivated by the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 89-95 31409770-8 2019 Rapamycin inhibited both mTORC1 and mTORC2 activation, whereas p62 siRNA inhibited only mTORC1 activation and maintained mTORC2 and Akt activation. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 25-31 31116586-1 2019 Everolimus inhibits mammalian target of rapamycin complex 1 (mTORC1) and is known to cause induction of autophagy and G1 cell cycle arrest. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 61-67 31142473-9 2019 In addition, the mammalian target of rapamycin complex 1 (mTORC1) pathway was remarkably activated in lupus AtMs, and blocking mTORC1 signalling by rapamycin abolished the generation of T-bet+ B cells and terminal differentiation of lupus AtMs. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 127-133 30676865-4 2019 Current evidence suggests that for acute contraction models of mechanical stimuli, there is an emerging pattern suggesting that there is an early increase in protein synthesis governed by a rapamycin-sensitive mTORC1-dependent mechanism, while at later poststimulation time points, the mechanism may change to a rapamycin-insensitive mTORC1-dependent or even an mTORC1-independent mechanism. Sirolimus 190-199 CREB regulated transcription coactivator 1 Mus musculus 210-216 31091421-5 2019 Additionally, increased mammalian target of rapamycin complex 1 (mTORC1) activity is observed in the Lkb1 conditional knockout (cKO) chondrocytes, and rapamycin (mTORC1 inhibitor) treatment significantly alleviates the expansion of growth-plate cartilage and eliminates the enchondroma-like lesions in Lkb1 cKO mice. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 65-71 31091421-5 2019 Additionally, increased mammalian target of rapamycin complex 1 (mTORC1) activity is observed in the Lkb1 conditional knockout (cKO) chondrocytes, and rapamycin (mTORC1 inhibitor) treatment significantly alleviates the expansion of growth-plate cartilage and eliminates the enchondroma-like lesions in Lkb1 cKO mice. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 162-168 31091421-5 2019 Additionally, increased mammalian target of rapamycin complex 1 (mTORC1) activity is observed in the Lkb1 conditional knockout (cKO) chondrocytes, and rapamycin (mTORC1 inhibitor) treatment significantly alleviates the expansion of growth-plate cartilage and eliminates the enchondroma-like lesions in Lkb1 cKO mice. Sirolimus 151-160 CREB regulated transcription coactivator 1 Mus musculus 65-71 31091421-5 2019 Additionally, increased mammalian target of rapamycin complex 1 (mTORC1) activity is observed in the Lkb1 conditional knockout (cKO) chondrocytes, and rapamycin (mTORC1 inhibitor) treatment significantly alleviates the expansion of growth-plate cartilage and eliminates the enchondroma-like lesions in Lkb1 cKO mice. Sirolimus 151-160 CREB regulated transcription coactivator 1 Mus musculus 162-168 30676865-4 2019 Current evidence suggests that for acute contraction models of mechanical stimuli, there is an emerging pattern suggesting that there is an early increase in protein synthesis governed by a rapamycin-sensitive mTORC1-dependent mechanism, while at later poststimulation time points, the mechanism may change to a rapamycin-insensitive mTORC1-dependent or even an mTORC1-independent mechanism. Sirolimus 190-199 CREB regulated transcription coactivator 1 Mus musculus 334-340 30676865-4 2019 Current evidence suggests that for acute contraction models of mechanical stimuli, there is an emerging pattern suggesting that there is an early increase in protein synthesis governed by a rapamycin-sensitive mTORC1-dependent mechanism, while at later poststimulation time points, the mechanism may change to a rapamycin-insensitive mTORC1-dependent or even an mTORC1-independent mechanism. Sirolimus 190-199 CREB regulated transcription coactivator 1 Mus musculus 334-340 30676865-4 2019 Current evidence suggests that for acute contraction models of mechanical stimuli, there is an emerging pattern suggesting that there is an early increase in protein synthesis governed by a rapamycin-sensitive mTORC1-dependent mechanism, while at later poststimulation time points, the mechanism may change to a rapamycin-insensitive mTORC1-dependent or even an mTORC1-independent mechanism. Sirolimus 312-321 CREB regulated transcription coactivator 1 Mus musculus 210-216 31353861-8 2019 Tsc1 gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by RHEB1 gene deletion or rapamycin treatment. Sirolimus 167-176 CREB regulated transcription coactivator 1 Mus musculus 58-64 31211512-7 2019 Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment may act in part through TCR-mediated mammalian target of rapamycin complex 1 (mTORC1) signalling activation. Sirolimus 129-138 CREB regulated transcription coactivator 1 Mus musculus 150-156 31189691-6 2019 To better characterize the connection between these two pathways, we performed a phosphoproteome analysis of ER-positive MCF7 breast cancer cells treated with estrogen or estrogen and the mTORC1 inhibitor rapamycin. Sirolimus 205-214 CREB regulated transcription coactivator 1 Mus musculus 188-194 31363142-6 2019 AVF in mice treated with rapamycin had reduced Akt1 and mTORC1 but not mTORC2 phosphorylation. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 56-62 31354497-9 2019 In addition, rapamycin was used to inhibit mTORC1 signaling, and it was found that colon length, disease associated index (DAI), and proportion of Treg cells of mice in the rapamycin-DSS group were not different from those of mice in the rapamycin/berberine-DSS group. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 43-49 31042058-2 2019 Proproliferative mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2) are activated in the kidneys of mice with PKD. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 75-81 31042058-3 2019 Sirolimus indirectly inhibits mTORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 30-36 31157925-3 2019 However, recent work has recognized the inhibitory impact this spatial redistribution has on mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of metabolism. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 136-142 31324799-0 2019 A novel rapamycin analog is highly selective for mTORC1 in vivo. Sirolimus 8-17 CREB regulated transcription coactivator 1 Mus musculus 49-55 31324799-1 2019 Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 70-76 31324799-1 2019 Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 70-76 31324799-3 2019 Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 104-110 31319820-9 2019 Using these as initial readouts, we identified rich media conditions that promoted rapid cell growth but, upon mTORC1 inactivation by rapamycin, led to a growth/development switch. Sirolimus 134-143 CREB regulated transcription coactivator 1 Mus musculus 111-117 31042058-10 2019 In conclusion, torin2 and sirolimus were equally effective in decreasing cyst burden and improving kidney function and mediated comparable effects on mTORC1 and mTORC2 signaling and proliferation in the Pkd1RC/RC kidney. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 150-156 31112404-2 2019 For instance, specific inhibition of mTORC1 by treating Sertoli cells with rapamycin promotes the Sertoli cell barrier, making it "tighter." Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 37-43 31005665-0 2019 Nicotine inhibits rapamycin-induced pain through activating mTORC1/S6K/IRS-1-related feedback inhibition loop. Sirolimus 18-27 CREB regulated transcription coactivator 1 Mus musculus 60-66 31005665-1 2019 Mammalian target of rapamycin complex 1 (mTORC1) inhibitors increase the incidence of pain in patients, and this finding has been replicated in animal models. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 41-47 30956113-1 2019 The mechanistic target of rapamycin complex (mTORC1) is a signaling hub on the lysosome surface, responding to lysosomal amino acids. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 45-51 31044492-1 2019 Insulin, insulin-like growth factor-1 (IGF-1) and essential amino acids activate the mechanistic target of rapamycin complex 1 (mTORC1), the main nutrient-sensitive kinase. Sirolimus 107-116 CREB regulated transcription coactivator 1 Mus musculus 128-134 31234465-5 2019 In older men, we observed an inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) in the highly viable spermatozoa population. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 90-96 30917412-5 2019 The effect of NR is blocked by the mTORC1 inhibitor rapamycin or the SIRT1 inhibitor EX527. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 35-41 30892080-6 2019 Furthermore, we found that pharmacological inhibition of the mTORC1 complex with rapamycin not only restored mitochondrial homeostasis but also reduced cellular senescence to bleomycin in lung epithelial cells. Sirolimus 81-90 CREB regulated transcription coactivator 1 Mus musculus 61-67 31312666-8 2019 Interestingly, we observed that mTORC1 inhibition with rapamycin improved myogenic and chondrogenic differentiation and reduced levels of apoptosis and senescence in Zmpste24 -/- MDSPCs. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 32-38 30903363-4 2019 The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin complex 1 (mTORC1), but AMPK-independent effects of metformin have also been described. Sirolimus 195-204 CREB regulated transcription coactivator 1 Mus musculus 216-222 31033201-3 2019 The agent also stimulates AMP-activated protein kinase (AMPK) and consequently influences the mammalian target of rapamycin complex 1 (mTORC1) pathways. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 135-141 30798505-2 2019 The state of senescence is controlled by extensive rewiring of signalling pathways, at the heart of which lies the mammalian Target of Rapamycin Complex I (mTORC1). Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 156-162 31060359-5 2019 Rapamycin, a specific inhibitor of mTORC1, downregulated 4EBP1 phosphorylation and the expression of PPARgamma and the following lipogenic genes: lipin 1, DGAT1, ACC, and FAS. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 35-41 30527742-1 2019 Although emerging evidence indicates an important role of the circadian clock in modulating the diurnal oscillation of mammalian target of rapamycin complex 1 (mTORC1) signaling, the underlying molecular mechanism remains elusive. Sirolimus 139-148 CREB regulated transcription coactivator 1 Mus musculus 160-166 30952607-5 2019 Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8+ T cell death. Sirolimus 118-127 CREB regulated transcription coactivator 1 Mus musculus 139-145 31133888-7 2019 Low-dose rapamycin (0.1 nM) normalized respiration with the magnitude of this normalization greater for AD-A LCLs, suggesting that the mammalian target of rapamycin complex 1 (mTORC1) pathway may have a different dynamic range for regulating mitochondrial activity in individuals with ASD with and without mitochondrial dysfunction, potentially related to S6K1 (S6 kinase beta-1) regulation. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 176-182 30835510-1 2019 Previous studies established that leucine stimulates protein synthesis in skeletal muscle to the same extent as a complete mixture of amino acids, and the effect occurs through activation of the mechanistic target of rapamycin in complex 1 (mTORC1). Sirolimus 217-226 CREB regulated transcription coactivator 1 Mus musculus 241-247 30923110-8 2019 Inhibition of mTORC1 with rapamycin decreases protein synthesis and ubiquitin accumulation in UCH-L1-deficient neurons. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 14-20 31327863-7 2019 In addition, in vitro study showed that ablation of Tsc2 promoted the development of intestinal organoids without epidermal growth factor, while mTORC1 inhibitor, rapamycin, diminished this phenotype. Sirolimus 163-172 CREB regulated transcription coactivator 1 Mus musculus 145-151 30988224-3 2019 As the hamartin-tuberin-complex downregulates the mechanistic/mammalian target of the rapamycin complex1 (mTORC1), dysfunction in either hamartin or tuberin induces the constitutive activation of mTORC1. Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 106-112 30988224-3 2019 As the hamartin-tuberin-complex downregulates the mechanistic/mammalian target of the rapamycin complex1 (mTORC1), dysfunction in either hamartin or tuberin induces the constitutive activation of mTORC1. Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 196-202 30663221-4 2019 Ibr-7 was observed to dramatically suppress the mammalian target of Rapamycin complex 1 (mTORC1)/S6 signaling pathway, which is only slightly affected by ibrutinib, thus accounting for the superior anti-cancer activity of Ibr-7 towards NSCLC. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 89-95 30910807-3 2019 Here, single-cell measurements of signal transduction intermediates in the mechanistic target of rapamycin complex 1 (mTORC1) pathway reveal that ventral NSPCs have higher levels of signaling than dorsal NSPCs. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 118-124 31182914-0 2019 Feedback Activation of SGK3 and AKT Contributes to Rapamycin Resistance by Reactivating mTORC1/4EBP1 Axis via TSC2 in Breast Cancer. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 88-94 31182914-1 2019 The mTORC1 inhibitors, such as rapamycin and its analogs, show limited antitumor activity in clinic, reasons for which have not been clearly elucidated. Sirolimus 31-40 CREB regulated transcription coactivator 1 Mus musculus 4-10 31072927-1 2019 During skeletal muscle regeneration, muscle stem cells (MuSCs) respond to multiple signaling inputs that converge onto mammalian target of rapamycin complex 1 (mTORC1) signaling pathways. Sirolimus 139-148 CREB regulated transcription coactivator 1 Mus musculus 160-166 31113850-5 2019 We further delineated the signaling pathways involved and showed that TGF-beta1-induced ATF4 production depended on cooperation between canonical TGF-beta1 signaling through Smad3 and activation of mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Sirolimus 220-229 CREB regulated transcription coactivator 1 Mus musculus 241-247 31092879-6 2019 Impaired activation of Akt increased mRNA expression of the muscle atrophy F-Box (MAFbx), decreased activation of the mammalian Target of Rapamycin Complex 1 (mTORC1) and stimulated apoptosis by impairing the Ser9 phosphorylation of glycogen synthase kinase 3beta. Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 159-165 31010692-11 2019 However, a search of more effective way to target mTOR has generated a third generation inhibitor of mTOR, "Rapalink", that bivalently combines rapamycin with an ATP-binding inhibitor, which effectively abolishes the mTORC1 activity. Sirolimus 144-153 CREB regulated transcription coactivator 1 Mus musculus 217-223 32694720-1 2019 The protein kinase complex mechanistic target of rapamycin complex 1 (mTORC1) serves as a key conduit between growth signals and the metabolic processes underlying cell growth. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 70-76 30563829-4 2019 To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer. Sirolimus 112-121 CREB regulated transcription coactivator 1 Mus musculus 93-99 30563829-8 2019 Rapamycin significantly inhibited tumor mTORC1, shown by decreased rpS6 phosphorylation in treated versus control patients (P = 0.008). Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 40-46 30145794-1 2019 The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 70-76 30665937-2 2019 In this study, myeloid cell-specific Raptor knockout (KO) mice were used to determine the roles of mechanistic target of rapamycin complex 1 (mTORC1) in regulating macrophage function from Lewis lung carcinoma (LLC) s.c. tumors and lung tumor metastasis. Sirolimus 121-130 CREB regulated transcription coactivator 1 Mus musculus 142-148 30650200-7 2019 The OSI-027 treatment of keloid keratinocytes showed more effectively inhibited cell proliferation and migration compared to the mTORC1 inhibitor, rapamycin. Sirolimus 147-156 CREB regulated transcription coactivator 1 Mus musculus 129-135 30795552-4 2019 Mammalian (or mechanistic) target of rapamycin (mTOR) is a conserved serine/threonine kinase belonging to the phosphatidylinositol 3-kinase (PI3K)-related kinase family (PIKK) and resides in two distinct signalling complexes named mTORC1, involved in mRNA translation and protein synthesis and mTORC2 that controls cell survival and migration. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 231-237 30791416-6 2019 Pharmacological activation of autophagy is typically achieved by blocking the kinase activity of mammalian target of rapamycin (mTOR) enzymatic complex 1 (mTORC1), removing its autophagy suppressor activity observed under physiological conditions; acting in this way, rapamycin provided the first proof of principle that pharmacological autophagy enhancement can induce neuroprotection through the facilitation of oligomers" clearance. Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 155-161 30728291-2 2019 TSC is caused by inactivating mutations in the genes encoding TSC1/2, negative regulators of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 138-144 30863496-14 2019 Thus, Rapamycin reduces HB in a clinically relevant model driven by beta-catenin and Yap1, supporting use of mTORC1 inhibitors in their therapy. Sirolimus 6-15 CREB regulated transcription coactivator 1 Mus musculus 109-115 30967006-3 2019 Consistent with this idea, activation of the metabolic regulator mechanistic target of rapamycin complex-1 (mTORC1) in response to acute stimulation by growth factors and extracellular amino acids requires internalization of amino acids by macropinocytosis. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 108-114 30514904-1 2019 Mechanistic target of rapamycin mTOR complex 1 (mTORC1) plays a key role in the integration of various environmental signals to regulate cell growth and metabolism. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 48-54 30698725-5 2019 Blood and muscle biopsies were collected over 360 min during recovery from exercise to assess MyoPS and MitoPS rates and signaling through mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 159-168 CREB regulated transcription coactivator 1 Mus musculus 180-186 29761287-6 2019 The expression of inflammation markers, bone structure-associated proteins and mammalian target of rapamycin complex1 (mTORC1) pathway-related proteins was assessed by immunohistochemical staining. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 119-125 30640966-7 2019 The allosteric inhibitor rapamycin only partially suppressed mTORC1 activity and exhibited a minimal effect on the induction of profibrotic markers. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 61-67 30622053-9 2019 Consistently, rapamycin alone or rapamycin in combination with either 3-BrPA or CB-839 had stronger inhibitory effects on mTORC1 and proliferation of tumor cells than combination of 3-BrPA and CB-839. Sirolimus 14-23 CREB regulated transcription coactivator 1 Mus musculus 122-128 30622053-9 2019 Consistently, rapamycin alone or rapamycin in combination with either 3-BrPA or CB-839 had stronger inhibitory effects on mTORC1 and proliferation of tumor cells than combination of 3-BrPA and CB-839. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 122-128 30530594-5 2019 In this study, we used an in vitro murine model in which the mTORC1 inhibitor rapamycin, when added after a B cell has committed to divide, suppresses class switching while preserving proliferation. Sirolimus 78-87 CREB regulated transcription coactivator 1 Mus musculus 61-67 30507612-7 2019 Lipin 2/3 deficiency caused phosphatidic acid accumulation and mammalian target of rapamycin complex 1 (mTORC1) activation, which were associated with enhanced protein levels of a key phospholipid biosynthetic enzyme (CTP:phosphocholine cytidylyltransferase alpha) and altered membrane phospholipid composition. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 104-110 30602778-3 2019 Here we demonstrate that rapamycin-insensitive mTORC1 signaling via 4E-BP1 is a critical pathway for TGF-beta1 stimulated collagen synthesis in human lung fibroblasts, whereas canonical PI3K/Akt signaling is not required. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 47-53 30523518-3 2019 mTORC1 repression by rapamycin prior to irradiation, or metabolic activation by minocycline after irradiation, partially rescues neuroepithelium integrity, neurite-growing capacity, ventricle formation and extracellular acidification rate as an integral measure of metabolic output. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 0-6 30547365-1 2019 Previous studies showed that repeated intrathecal morphine injection activated the mammalian target of rapamycin complex 1 (mTORC1) in spinal dorsal horn neurons and that blocking this activation by intrathecal infusion of rapamycin, a specific mTORC1 inhibitor, prevented the initiation of morphine-induced tolerance and hyperalgesia. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 124-130 30547365-1 2019 Previous studies showed that repeated intrathecal morphine injection activated the mammalian target of rapamycin complex 1 (mTORC1) in spinal dorsal horn neurons and that blocking this activation by intrathecal infusion of rapamycin, a specific mTORC1 inhibitor, prevented the initiation of morphine-induced tolerance and hyperalgesia. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 245-251 30682771-6 2019 Rapalogs, such as sirolimus and everolimus, partially inhibit mTOR complex 1 (mTORC1) and exhibit anti-cancer activity in vitro and in vivo in BTC. Sirolimus 18-27 CREB regulated transcription coactivator 1 Mus musculus 78-84 30670706-3 2019 We hypothesized that mechanistic Target of Rapamycin Complex 1 (mTORC1) is a positive regulator of key genes encoding Electron Transport Chain (ETC) proteins and stimulates oxidative phosphorylation in trophoblast and that ETC protein expression is down-regulated in placentas of infants with intrauterine growth restriction (IUGR). Sirolimus 43-52 CREB regulated transcription coactivator 1 Mus musculus 64-70 30705972-5 2019 Phosphorylation of p70 S6 kinase (p70S6K), an essential factor for promoting protein synthesis in skeletal muscle, was significantly increased by S42 to almost the same extent as by insulin, but this was significantly prevented by treatment with rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 246-255 CREB regulated transcription coactivator 1 Mus musculus 316-322 30670976-10 2018 Interestingly, by using pharmacological inhibition of the kinase mammalian target of rapamycin complex 1 (mTORC1) by Rapamycin, we were able to recapitulate similar changes in the proliferation dynamics of intestinal stem cells. Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 106-112 30904097-4 2019 Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 182-188 30904097-5 2019 Rapamycin, an mTORC1 inhibitor, is now the only pharmacological therapy approved for the treatment of TSC. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 14-20 30553437-8 2019 Rapamycin treatment in MT-COMP mice reduced mTORC1 signaling and intracellular retention of COMP, and increased proliferation, but did not change inflammatory markers IL-16 and eosinophil peroxidase. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 44-50 31379141-1 2019 The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to various environmental inputs, especially amino acids. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 31840789-5 2019 Many protein associations and regulatory pathways for mTORC1 and mTORC2 in Dictyostelium have context similarity to mammalian cells and specificity to inhibition by the immunosuppressive drug rapamycin. Sirolimus 192-201 CREB regulated transcription coactivator 1 Mus musculus 54-60 31840789-6 2019 In Dictyostelium, mTORC1 function is inactivated upon starvation-induced development, but development is directly induced through rapamycin-mediated inhibition of mTORC1 activity, even in the absence of nutrient withdrawal. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 163-169 30335577-2 2019 A large body of work shows that a mammalian target of rapamycin complex 1 (mTORC1)-mediated increase of muscle protein synthesis is the key, but not sole, mechanism by which resistance exercise causes muscle hypertrophy. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 75-81 30838925-9 2019 This beneficial compensatory remodeling of cortical GABAergic innervation is mechanistic target of rapamycin complex 1 (mTORC1)-dependent, and its inhibition with rapamycin leads to a striking increase in motor seizures. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 120-126 30932134-1 2019 BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is fundamental for many cellular processes, yet it is often dysregulated with aging. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 57-63 30365078-0 2018 Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 113-119 30546014-2 2018 TFEB activity is inhibited following its phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) on the surface of the lysosome. Sirolimus 80-89 CREB regulated transcription coactivator 1 Mus musculus 101-107 30144045-11 2018 A higher cathepsin activity, particularly of cathepsin B, was observed, which was reduced by mTORC1 inhibition with rapamycin in vivo. Sirolimus 116-125 CREB regulated transcription coactivator 1 Mus musculus 93-99 30410117-1 2018 Although rapamycin is a well-known conformational inhibitor of mTORC1, it is now widely used for treating arterial restenosis. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 63-69 30348864-2 2018 Using two-photon fluorescence lifetime microscopy of the coenzymes, NADH and NADPH, and tracking brain oxygen metabolism with multi-parametric photoacoustic microscopy, we show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Sirolimus 228-237 CREB regulated transcription coactivator 1 Mus musculus 249-255 30341150-8 2018 Further analysis showed that platelet microparticles activated the mammalian target of rapamycin complex 1 (mTORC1) pathway in glomerular endothelial cells; inhibition of the mTORC1 pathway by rapamycin or raptor siRNA significantly protected against microparticle-induced glomerular endothelial injury in vivo and in vitro. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 108-114 30309855-5 2018 This stark difference supports the idea that inhibition of mTORC1 by rapamycin has a key role in the improvement of the mitochondrial function in Cox15 sm/sm muscle. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 59-65 30117227-11 2018 We administered continuous rapamycin, a specific mTORC1 inhibitor, orally to C57BL/6J mice concurrently with a high-fat, high-sucrose (HFHS) diet for 20 weeks. Sirolimus 27-36 CREB regulated transcription coactivator 1 Mus musculus 49-55 30061014-1 2018 BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of large vessel vasculitis (LVV) pathogenesis. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 53-60 30061014-9 2018 Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4+IFNgamma+, CD4+IL17+ and CD4+IL21+ T cells in patients with LVV. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 14-20 30247156-3 2018 Here, we demonstrate that mTORC1 signaling is highly and specifically activated in the cochlear neurosensory epithelium (NSE) in aging mice, and rapamycin injection prevents ARHL. Sirolimus 145-154 CREB regulated transcription coactivator 1 Mus musculus 26-32 29928901-3 2018 In this study, we sought to understand the neuroprotective effect of rapamycin, the selective inhibitor of mTORC1, on RGC survival and the cellular mechanics that mediate this effect. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 107-113 30341150-8 2018 Further analysis showed that platelet microparticles activated the mammalian target of rapamycin complex 1 (mTORC1) pathway in glomerular endothelial cells; inhibition of the mTORC1 pathway by rapamycin or raptor siRNA significantly protected against microparticle-induced glomerular endothelial injury in vivo and in vitro. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 175-181 29969175-6 2018 Also, our results suggest that mTORC1 pathway overactivation may function as a second hit event contributing to downregulation of the Reelin-DAB1 cascade in patient-derived NPCs, and that inhibition of mTORC1 by rapamycin attenuates Reelin-DAB1 signaling impairment. Sirolimus 212-221 CREB regulated transcription coactivator 1 Mus musculus 31-37 30326670-2 2018 mTOR functions in two distinct complexes-mTORC1 is sensitive to rapamycin, while, mTORC2 is insensitive to this drug. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 41-47 30232410-4 2018 These two proteins form a complex that negatively regulates mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cellular growth and metabolism. Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 103-109 29969175-6 2018 Also, our results suggest that mTORC1 pathway overactivation may function as a second hit event contributing to downregulation of the Reelin-DAB1 cascade in patient-derived NPCs, and that inhibition of mTORC1 by rapamycin attenuates Reelin-DAB1 signaling impairment. Sirolimus 212-221 CREB regulated transcription coactivator 1 Mus musculus 202-208 30144504-2 2018 The TSC1 and TSC2 genes encode proteins forming a complex (TSC), which is a major regulator and suppressor of mammalian target of rapamycin complex 1 (mTORC1), a signaling complex that promotes cell growth and proliferation. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 151-157 30058583-9 2018 Results: The beneficial effects of rapamycin on neuropathic pain were attributed to a reduction in mammalian target of rapamycin sensitive complex 1 (mTORC1)-positive cells (70.80 +- 2.41 vs. 112.30 +- 5.66, F = 34.36, P < 0.01) and mTORC1 activity in the mouse spinal cord. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 150-156 30258985-2 2018 Although rapamycin inhibits the two canonical mTOR complexes, mTORC1 and mTORC2, it often shows minimal benefit as an anticancer drug. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 62-68 30087333-5 2018 Knockout of either TSC1 or DEPDC5 led to enhanced HIV-1 reactivation in both a T-cell line (C11) and a monocyte cell line (U1), and this enhancement could be antagonized by the mTORC1 inhibitor rapamycin. Sirolimus 194-203 CREB regulated transcription coactivator 1 Mus musculus 177-183 30242175-1 2018 Tuberous Sclerosis Complex (TSC), a rare genetic disorder with mechanistic target of rapamycin complex 1 (mTORC1) hyperactivation, is characterized by multi-organ hamartomatous benign tumors including brain, skin, kidney, and lung (Lymphangioleiomyomatosis). Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 106-112 30206977-4 2018 The inactivation of mTORC1 by rapamycin pretreatment or rotenone-induced mitochondrial complex inhibition showed a similar effect because of the metformin treatment on the proliferation and apoptosis of HaCaT keratinocytes. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 20-26 30048010-7 2018 This beneficial compensatory remodeling of cortical GABAergic innervation is mTORC1-dependent and its inhibition with rapamycin leads to a striking increase in motor seizures. Sirolimus 118-127 CREB regulated transcription coactivator 1 Mus musculus 77-83 29885404-3 2018 Sirolimus, an inhibitor of mTOR complex 1 (mTORC1), slows down disease progression in some, but not all patients. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 43-49 30107854-9 2018 Activation of mTORC1, TGF-beta and NF-kappaB signaling pathways was determined in irradiated renal tissues, which were inhibited by rapamycin treatment. Sirolimus 132-141 CREB regulated transcription coactivator 1 Mus musculus 14-20 30107854-13 2018 CONCLUSIONS: These findings indicate that inhibition of mTORC1 signaling by rapamycin ameliorates irradiation-induced renal toxicity mediated by decreasing cellular apoptosis and increasing CD133+ renal stem-like cells. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 56-62 30219159-13 2018 Furthermore, in vitro studies revealed that the inhibitory effect of rapamycin on the angiogenic ability of HUVECs and its significant inhibitory effects on the protein level of HIF-1alpha and the phosphorylation of proteins involved in the mTORC1 pathway, including mTOR, raptor and p70S6K (P < 0.05), were enhanced by cotreatment with SRT1720 and rapamycin (P < 0.05). Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 241-247 30058583-9 2018 Results: The beneficial effects of rapamycin on neuropathic pain were attributed to a reduction in mammalian target of rapamycin sensitive complex 1 (mTORC1)-positive cells (70.80 +- 2.41 vs. 112.30 +- 5.66, F = 34.36, P < 0.01) and mTORC1 activity in the mouse spinal cord. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 236-242 29607465-0 2018 Sirolimus enhances remission induction in patients with high risk acute myeloid leukemia and mTORC1 target inhibition. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 93-99 29738849-10 2018 Involvement of mechanistic target of rapamycin complex-1 (mTORC1) signaling was also demonstrated, as the sustained antidepressant effects of LY341495 was attenuated by intra-mPFC injection of rapamycin, an mTORC1 inhibitor. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 58-64 30050079-7 2018 Furthermore, co-inhibition of mTORC1 and HDAC with rapamycin and valproic acid, but neither alone, reproducibly promoted ESR1 expression in TNBC cells. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 30-36 29357413-7 2018 Short-term treatment of CKD mice with rapamycin, an inhibitor of mTORC1, or tauroursodeoxycholic acid, a bile acid that restores ER homeostasis, normalized mTORC1 activity, molecular markers of UPR, and calcium content of aortas. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 65-71 30050412-7 2018 Interestingly, injection of Rapamycin, a pharmacological mTORC1 inhibitor, to pregnant mothers increased the lifespan of the mutant offspring, restored myelination as well as the levels of Qk and NfascNF155, and consequently the organization of the paranodal domains. Sirolimus 28-37 CREB regulated transcription coactivator 1 Mus musculus 57-63 29635516-1 2018 Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental disorder and the quintessential disorder of mechanistic Target of Rapamycin Complex 1 (mTORC1) dysregulation. Sirolimus 143-152 CREB regulated transcription coactivator 1 Mus musculus 164-170 29337352-2 2018 Here, we report in mice that L-LTP failure induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2alpha (eIF2alpha). Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 113-119 29884898-5 2018 Infusion of a selective mTORC1 inhibitor, rapamycin, into the dorsal hippocampus 15 or 40 min but not 3 h before testing at 24 h reversibly disrupted memory expression even in animals that had already expressed IA memory. Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 24-30 29357413-7 2018 Short-term treatment of CKD mice with rapamycin, an inhibitor of mTORC1, or tauroursodeoxycholic acid, a bile acid that restores ER homeostasis, normalized mTORC1 activity, molecular markers of UPR, and calcium content of aortas. Sirolimus 38-47 CREB regulated transcription coactivator 1 Mus musculus 156-162 29844054-4 2018 Upstream stimuli from various metabolic activities converge on mechanistic target of rapamycin complex 1 (mTORC1), and aberrant mTORC1 signaling is implicated in aging and age-related degeneration of the RPE. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 106-112 29559472-7 2018 Collectively, our data support a model in which Plk1, instead of AKT, regulates the TSC/mTORC1 pathway during mitosis, eventually regulating the efficacy of rapamycin.Significance: This seminal report shows that activation of mTORC1 can be independent of AKT during mitosis. Sirolimus 157-166 CREB regulated transcription coactivator 1 Mus musculus 226-232 29481864-7 2018 mTORC1-dependent effects of DEPDC5/NPRL3 KD were determined using the mTOR inhibitor rapamycin. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 0-6 29859856-6 2018 Inhibition of ileal mTORC1 signaling by rapamycin significantly attenuated the stimulation of bile acid secretion, TGR5 expression and GLP-1 synthesis induced by RYGB in lean and diet-induced obese mice. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 20-26 29364507-2 2018 This disorder is characterized by increased activity of mammalian target of rapamycin complex 1 (mTORC1), which is involved in regulating ribosomal biogenesis and translation initiation. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 97-103 29786082-3 2018 Moreover, rapamycin blocks mGluR-LTD in mTORC1-deficient mice. Sirolimus 10-19 CREB regulated transcription coactivator 1 Mus musculus 40-46 29731844-4 2018 The results demonstrated that combined treatment with rapamycin and resveratrol effectively inhibited cell viability in the MM1.S cell line through inhibition of the mTORC1 and mTORC2 signaling pathways, compared with resveratrol or rapamycin monotherapy. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 166-172 29483210-8 2018 Finally, proliferation of NSGCT cells in vitro and in vivo is significantly inhibited by combined treatment with the clinically available agents erlotinib and rapamycin, which target EGFR and mTORC1 signaling, respectively. Sirolimus 159-168 CREB regulated transcription coactivator 1 Mus musculus 192-198 29757673-5 2018 Results indicated that both rapamycin and AZD8055 inhibited mTOR complex 1 (mTORC1)/70-kDa ribosomal protein S6 kinase signaling similarly, whereas mTORC1/eukaryotic translation initiation factor 4E-binding protein 1 signaling was greatly inhibited by AZD8055. Sirolimus 28-37 CREB regulated transcription coactivator 1 Mus musculus 76-82 29758070-2 2018 mTORC1 is frequently activated in human cancers and, although the mTORC1 inhibitor rapamycin has a cytostatic effect, it is, in general, unable to elicit a robust curative effect or tumor regression. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 0-6 29758070-2 2018 mTORC1 is frequently activated in human cancers and, although the mTORC1 inhibitor rapamycin has a cytostatic effect, it is, in general, unable to elicit a robust curative effect or tumor regression. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 66-72 29744053-5 2018 Further study demonstrated that tunicamycin-induced cell death was enhanced by rapamycin, a specific inhibitor of mTORC1. Sirolimus 79-88 CREB regulated transcription coactivator 1 Mus musculus 114-120 29755689-11 2018 Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 46-52 29472548-1 2018 Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 120-126 29761115-7 2018 These phenotypic features persisted throughout embryonic development and were significantly reduced upon treatment with the mTORC1 inhibitor, rapamycin, as well as overexpression of human WT DEPDC5 transcript. Sirolimus 142-151 CREB regulated transcription coactivator 1 Mus musculus 124-130 29241828-2 2018 Several recent studies in genetic mouse models of FOP support involvement of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the pathophysiology of FOP and propose the repurposed use of rapamycin, an inhibitor of mTORC1 signaling in clinical trials for the management of FOP. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 124-130 29506489-9 2018 This technique further showed that the inhibition of AKT1 signaling is phenocopied by blocking the mTORC1 pathway with rapamycin. Sirolimus 119-128 CREB regulated transcription coactivator 1 Mus musculus 99-105 29161463-14 2018 In turn, blockade of mTORC1 by 3-day rapamycin treatment enhanced transforming growth factor beta production, while dual blockade of mTORC1 and mTORC2 by 4-week rapamycin treatment induced autophagy, restored the expression of GATA-3 and CTLA-4, and corrected Treg cell function. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 21-27 29080681-5 2018 By contrast, abrogation of mTORC1 by rapamycin completely reversed the reduced pigmentation, and alleviation of endoplasmic reticulum stress by SMER28 or 4-phenylbutyrate (PBA) or alleviation of mitochondrial oxidative stress by administration of adenosine triphosphate partially reversed the reduced pigmentation in these mice. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 27-33 29396369-8 2018 Administration of B-type natriuretic peptide (BNP) to mice induced Ucp1 expression in inguinal adipose tissue in vivo, which was completely blocked by the mTORC1 inhibitor rapamycin. Sirolimus 172-181 CREB regulated transcription coactivator 1 Mus musculus 155-161 29692710-7 2018 We provide further insights that explain the reasons for the failure of numerous clinical trials conducted to date targeting PI3K or mTOR complex 1 (mTORC1) with rapamycin and its analogs. Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 149-155 29686643-3 2018 We show that rapamycin, which acts as an allosteric inhibitor of mTORC1, counteracts the impairment of novel object recognition. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 65-71 29344639-4 2018 In addition, western blot analysis indicated that PP242 completely inhibited mTORC1 and mTORC2 downstream signaling activities, whereas rapamycin only partially inhibited mTORC1 activity within LECs. Sirolimus 136-145 CREB regulated transcription coactivator 1 Mus musculus 171-177 28334166-6 2018 Inhibition of the overactivated mTORC1-S6K signaling pathway by rapamycin or mGluR5 antagonist ameliorated the deficiency of the excitatory synaptic transmission in the mPFC and the social recognition of Grk5-/- mice. Sirolimus 64-73 CREB regulated transcription coactivator 1 Mus musculus 32-38 29224866-8 2018 Inhibition of mTORC1 by rapamycin attenuated the phosphorylation of molecules related to mTORC1 signaling and caused a marked decrease in LAT1 expression in the cultured cells; expression of beta-casein also decreased significantly. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 28407241-3 2018 Isolated rat TDSCs were treated with various concentrations of leptin in the presence or absence of mTORC1 signaling specific inhibitor rapamycin in vitro. Sirolimus 136-145 CREB regulated transcription coactivator 1 Mus musculus 100-106 29224866-8 2018 Inhibition of mTORC1 by rapamycin attenuated the phosphorylation of molecules related to mTORC1 signaling and caused a marked decrease in LAT1 expression in the cultured cells; expression of beta-casein also decreased significantly. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 89-95 29233655-10 2018 Treating rats with rapamycin blocked the mTORC1 pathway and masked the abovementioned effects of rhEPO. Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 41-47 28300280-0 2018 Rapamycin attenuates BAFF-extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B-lymphoid cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 80-86 29389967-10 2018 Furthermore, BEZ235 resistance was suppressed by RAPTOR depletion, or allosteric mTORC1 inhibitor rapamycin. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 81-87 29375310-6 2017 We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 44-50 29283439-2 2018 Although the physiological function of TBCK remains unclear, loss-of-function mutations are associated with inhibition of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 144-153 CREB regulated transcription coactivator 1 Mus musculus 165-171 29190625-3 2018 Inhibition of the mTOR complex 1 (mTORC1) with rapamycin is currently the only known pharmacological treatment that increases lifespan in all model organisms studied. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 34-40 28300280-5 2018 Also, PP242, an mTORC1/2 kinase inhibitor, repressed survivin expression, and cell proliferation/viability more potently than rapamycin (mTORC1 inhibitor) in B cells in response to hsBAFF. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 137-143 29090333-10 2018 Intraperitoneal rapamycin (an mTORC1 inhibitor; 10 mg/kg) blocked the antidepressant effect of intracerebroventricular RvE1. Sirolimus 16-25 CREB regulated transcription coactivator 1 Mus musculus 30-36 29191929-0 2018 Correction: Inhibition of mTORC1 Kinase Activates Smads 1 and 5 but Not Smad8 in Human Prostate Cancer Cells, Mediating Cytostatic Response to Rapamycin. Sirolimus 143-152 CREB regulated transcription coactivator 1 Mus musculus 26-32 29238469-9 2017 Conclusion: Sirolimus can reduce proteinuria and alleviate the early DN podocyte injury in diabetic rat model by inhibiting the activity of mTORC1; but in the advanced stage of DN, sirolimus can increase podocyte injury and urine protein level. Sirolimus 12-21 CREB regulated transcription coactivator 1 Mus musculus 140-146 29106387-5 2017 Moreover, inhibition of mTORC1 signaling in alphaRaptorKO mice and in WT animals exposed to chronic rapamycin administration decreased glucagon content and glucagon secretion. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 24-30 29019741-7 2017 Inhibition of mTORC1 by rapamycin treatment increased radiation-induced cell apoptosis, reduced cell proliferation and delayed restoration of Wnt signaling in the hair matrix after radiation injury, leading to prolonged dystrophy and hair loss. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 28916721-5 2017 The hypertrophy-inducing mammalian target of rapamycin complex 1 (mTORC1) pathway was activated in Cpt2M-/- hearts; however, daily rapamycin exposure failed to attenuate hypertrophy in Cpt2M-/- mice. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 66-72 29170467-2 2017 However, mTORC1 inhibitors, such as rapamycin, have limited effectiveness as single agent cancer therapies, with feedback mechanisms inherent to the signaling network thought to diminish the anti-tumor effects of mTORC1 inhibition. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 9-15 29056426-1 2017 The mechanistic target of rapamycin complex 1 (mTORC1) supports proliferation through parallel induction of key anabolic processes, including protein, lipid, and nucleotide synthesis. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 47-53 28695335-13 2017 The mTORC1 inhibitor rapamycin (0.2 nmol/mouse, i.c.v.) Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 29021349-6 2017 We found that Akt-mTORC1 (mammalian target of rapamycin complex 1) signaling was increased, and treatment with 2.24 mg/kg d rapamycin or 40% caloric restriction for 9 weeks partially rescued cardiomyopathy or heart failure and restored autophagic flux in knockin mice. Sirolimus 46-55 CREB regulated transcription coactivator 1 Mus musculus 18-24 29061787-10 2017 Interestingly, the expression of P-gp was synergistically inhibited by combined treatment of U0126 with LY294002 and also inhibited by an mTORC1 inhibitor, rapamycin. Sirolimus 156-165 CREB regulated transcription coactivator 1 Mus musculus 138-144 28901376-6 2017 In addition, rapamycin, a selective mammalian target of rapamycin complex-1 (mTORC1) signaling pathway inhibitor, was employed to determine whether mechanical loading modulates heterotopic ossification in calcific tendinopathy through the mTORC1 signaling pathway. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 77-83 28827472-1 2017 The goal of the present study was to explore the protective effects of mTORC1 (mammalian target of rapamycin complex 1) inhibition by rapamycin on salt-induced hypertension and kidney injury in Dahl salt-sensitive (SS) rats. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 71-77 28637240-1 2017 Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 201-210 CREB regulated transcription coactivator 1 Mus musculus 222-228 28979705-7 2017 Furthermore, Rictor knockdown attenuated cell cycle progression and enhanced apoptosis, synergistic with treatment of mTORC1 inhibitor rapamycin owing to abrogating the feedback activation of Akt. Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 118-124 29340326-4 2018 Mammalian target of rapamycin complex 1 (mTORC1) inhibitors (e.g., sirolimus) have been found to be effective in treating TSC- or lymphangioleiomyomatosis-associated AML, but to date it is unknown whether this strategy is effective for sporadic AML. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 41-47 28701348-5 2017 Persistent induction of DNA double-strand breaks or mTORC1 inhibition by rapamycin results in reduced levels of HMO1 mRNA, but only in the presence of Tor1p. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 52-58 28808237-1 2017 Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 179-188 CREB regulated transcription coactivator 1 Mus musculus 200-206 28963126-8 2017 EGF stimulation of p70S6K was also independent of p-AKT Inhibition of the mTORC1 pathway with rapamycin abolished phosphorylation of p70S6K but had no effect on VEGF-A secretion, indicating that EGF-stimulated VEGF-A secretion did not require mTORC1 pathway activation. Sirolimus 94-103 CREB regulated transcription coactivator 1 Mus musculus 74-80 28963126-8 2017 EGF stimulation of p70S6K was also independent of p-AKT Inhibition of the mTORC1 pathway with rapamycin abolished phosphorylation of p70S6K but had no effect on VEGF-A secretion, indicating that EGF-stimulated VEGF-A secretion did not require mTORC1 pathway activation. Sirolimus 94-103 CREB regulated transcription coactivator 1 Mus musculus 243-249 28701309-10 2017 The abnormal SMC phenotype observed in the Arhgap18-/- mice can be partially rescued by pharmacological treatment with the mTORC1 inhibitor rapamycin, which reduces the synthetic and proinflammatory phenotype of Arhgap18-deficient SMC. Sirolimus 140-149 CREB regulated transcription coactivator 1 Mus musculus 123-129 28831455-2 2017 One potential and current model that explains Akt activation induced by the mTOR inhibitor rapamycin is the relief of mTORC1/p70S6K-mediated feedback inhibition of IRS-1/PI3K/Akt signaling, although this has not been experimentally proven. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 118-124 28768179-4 2017 mTORC1 inhibition by rapamycin downregulated all components of ISRmt, improved all MM hallmarks, and reversed the progression of even late-stage MM, without inducing mitochondrial biogenesis. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 0-6 29029388-0 2017 Rapamycin-induced miR-21 promotes mitochondrial homeostasis and adaptation in mTORC1 activated cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 78-84 28778941-5 2017 METHODS AND RESULTS: We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 34-40 28707282-3 2017 Clinical use of rapamycin is associated with several unwanted side effects, however, and several strategies are being taken to identify mTORC1 inhibitors with fewer side effects. Sirolimus 16-25 CREB regulated transcription coactivator 1 Mus musculus 136-142 28707282-5 2017 By testing compounds using a wild-type strain and isogenic cells lacking either TOR1 or FPR1, we can resolve not only whether a compound is an inhibitor of mTORC1 but also whether the inhibitor acts through a mechanism similar to rapamycin by binding Fpr1. Sirolimus 230-239 CREB regulated transcription coactivator 1 Mus musculus 156-162 28507054-8 2017 In contrast, rapamycin was able to decrease the androgen-mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake and prostate cancer cell growth. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 158-164 28244683-0 2017 Rapamycin treatment dose-dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell-cycle-associated CDK1/cyclin axis. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 99-105 28695825-4 2017 Abnormalities were blocked by the mTORC1 inhibitor sirolimus. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 34-40 28706237-8 2017 Treatment of OLETF with rapamycin, an mTORC1 inhibitor, partially restored autophagic activation in response to I/R and significantly attenuated I/R-induced renal injury. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 38-44 27264687-9 2017 In vivo OVA-Texo-stimulated CTLs upregulated the activities of the mTORC1 pathway-related molecules Akt, S6, eIF4E and T-bet, and treatment of the CTLs with an mTORC1 inhibitor, rapamycin, significantly reduced the OVA-Texo-induced increase in CTLs. Sirolimus 178-187 CREB regulated transcription coactivator 1 Mus musculus 67-73 28473248-9 2017 Moreover, autophagy inhibitor 3-MA could simulate the effects of TSC2 siRNA while autophagy inducer rapamycin could mimic the effects of raptor siRNA, suggesting that the beneficial effects of mTORC1 deletion were associated with autophagy induction. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 193-199 28578659-0 2017 Rapamycin (mTORC1 inhibitor) reduces the production of lactate and 2-hydroxyglutarate oncometabolites in IDH1 mutant fibrosarcoma cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 11-17 28696356-4 2017 The mTORC1 inhibitor rapamycin is a clinical approved immunosuppressant and several studies also verified its chondroprotective effects in OA. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 28696356-6 2017 Therefore, we aimed to investigate if inhibition of mTORC1 by rapamycin can preserve and sustain chondrocytes in an inflammatory environment. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 52-58 28696356-7 2017 Patient-derived chondrocytes were cultured in media supplemented with or without the mTORC1 inhibitor rapamycin. Sirolimus 102-111 CREB regulated transcription coactivator 1 Mus musculus 85-91 28903387-7 2017 Therefore, downregulated FOXO3a/PDGFRalpha/AKT pathway exerts a protective effect against hyperactivated mTORC1-induced tumorigenesis caused by loss of TSC1/TSC2 complex, and the combination of rapamycin and AG1295 may be a new effective strategy for TSC-associated tumors treatment. Sirolimus 194-203 CREB regulated transcription coactivator 1 Mus musculus 105-111 27923564-0 2017 Rapamycin preferentially inhibits human IL-5+ TH2-cell proliferation via an mTORC1/S6 kinase-1-dependent pathway. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 76-82 28424242-5 2017 By analyzing activated murine wild-type and Rheb-deficient CD4+ T cells, as well as murine CD4+ T cells activated in the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to identify six T-bet phosphorylation sites. Sirolimus 133-142 CREB regulated transcription coactivator 1 Mus musculus 173-179 28424242-6 2017 Five of these are novel, and four sites are consistently dephosphorylated in both Rheb-deficient CD4+ T cells and T cells treated with rapamycin, suggesting mTORC1 signaling controls their phosphorylation. Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 157-163 28214587-9 2017 The inhibitory effect of PAQR3 knockdown on autophagy is abrogated by rapamycin treatment, indicating that PAQR3 modulates autophagy via its regulation on mTORC1 signaling. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 155-161 28404689-6 2017 Pretreatment of human MCs using the mTORC1 inhibitor rapamycin, the mTORC1/mTORC2 inhibitor Torin1, or the two flavonoids decreases both gene expression and release (P < 0.0001) of all three mediators. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 36-42 28496990-6 2017 Inhibition of mTORC1 by rapamycin reduces T-cell expression of KIF13A and cell-surface M6PR, and increases T-cell survival in Listeria monocytogenes-infected mice. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 28250148-6 2017 Systemic rapamycin treatment, thought to selectively target mTOR complex 1 (mTORC1), suppressed mTOR/S6 signaling, reduced levels of MBP and overall tubulin, and decreased NF-H phosphorylation in nerves strained for 6 h, revealing a role for mTOR in increasing MBP expression and NF-H phosphorylation, and maintaining tubulin levels. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 76-82 27819676-7 2017 Inhibition of mTORC1 by rapamycin effectively attenuates the compensatory proliferation of hepatocytes in CAMK2gamma-/- livers. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 27634355-3 2017 The results demonstrate that a single dose of GLYX-13 rapidly activates the mTORC1 pathway in the prefrontal cortex (PFC), and that infusion of the selective mTORC1 inhibitor rapamycin into the medial PFC (mPFC) blocks the antidepressant behavioral actions of GLYX-13, indicating a requirement for mTORC1 similar to ketamine. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 158-164 27634355-3 2017 The results demonstrate that a single dose of GLYX-13 rapidly activates the mTORC1 pathway in the prefrontal cortex (PFC), and that infusion of the selective mTORC1 inhibitor rapamycin into the medial PFC (mPFC) blocks the antidepressant behavioral actions of GLYX-13, indicating a requirement for mTORC1 similar to ketamine. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 158-164 28323988-8 2017 These laminin alpha2 knockdown-mediated effects on F-actin and MT organization was blocked by exposing Sertoli cells to rapamycin, an inhibitor of mTORC1 signaling, and also SC79, an activator of Akt. Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 147-153 28938574-6 2017 GSK2126458 inhibited both PI3K and mTOR while rapamycin exerted stronger inhibitory effect on mTORC1 in renal tumours. Sirolimus 46-55 CREB regulated transcription coactivator 1 Mus musculus 94-100 28469768-6 2017 Of the three specific inhibitors, only rapamycin, an inhibitor of mTORC1, was found to inhibit FAK phosphorylation, suggesting that mTORC1 is the upstream regulator in shock-wave-elicited FAK phosphorylation. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 66-72 28469768-6 2017 Of the three specific inhibitors, only rapamycin, an inhibitor of mTORC1, was found to inhibit FAK phosphorylation, suggesting that mTORC1 is the upstream regulator in shock-wave-elicited FAK phosphorylation. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 132-138 28469768-9 2017 Besides, rapamycin was found to destruct the granular pattern of mTORC1, while dissociation between F-actin and mTORC1 was noted after cytochalasin D administration. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 65-71 28043916-7 2017 Additionally, ketamine and extinction exposure increased levels of mTORC1 in the medial prefrontal cortex (mPFC), a region involved in the acquisition and retrieval of extinction, and infusion of the selective mTORC1 inhibitor rapamycin into the mPFC blocked the effects of ketamine on extinction. Sirolimus 227-236 CREB regulated transcription coactivator 1 Mus musculus 67-73 28336152-5 2017 The gene products of TSC1/2 form a complex which at energy limiting states, down-regulates the activity of the regulator of protein synthesis, the mammalian target of rapamycin complex1 (mTORC1). Sirolimus 167-176 CREB regulated transcription coactivator 1 Mus musculus 187-193 28043916-7 2017 Additionally, ketamine and extinction exposure increased levels of mTORC1 in the medial prefrontal cortex (mPFC), a region involved in the acquisition and retrieval of extinction, and infusion of the selective mTORC1 inhibitor rapamycin into the mPFC blocked the effects of ketamine on extinction. Sirolimus 227-236 CREB regulated transcription coactivator 1 Mus musculus 210-216 28400999-7 2017 Rapamycin and its analogues (rapalogues) bind to the intercellular receptor FKBP12, and then predominantly inhibit mTORC1 signaling via an allosteric mechanism. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 115-121 28377693-5 2017 Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTORC1, in the IC of rats with neuropathic pain. Sirolimus 147-156 CREB regulated transcription coactivator 1 Mus musculus 174-180 28580286-8 2017 Rapamycin, an mTORC1 complex inhibitor, reduced the number and proliferation of pancreatic and endocrine progenitors. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 14-20 28292440-2 2017 Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 66-72 27935584-8 2017 Moreover, we showed that either knockdown of mTOR or inhibition of mTORC1 with rapamycin increases the expression of HMGCS2 in intestinal cells in vitro and in vivo, suggesting a possible cross-talk between mTOR and HMGCS2/betaHB signaling in intestinal cells. Sirolimus 79-88 CREB regulated transcription coactivator 1 Mus musculus 67-73 28278709-5 2017 Rapamycin, an mTORC1 inhibitor, showed similar effects to miR-185-5p. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 14-20 28469644-5 2017 In addition, we demonstrated alterations in mechanistic target of rapamycin complex 1 (mTORC1) signaling and functional rescue of the lifespan, locomotor defects and hypersensitivity to oxidative stress on treatment of GCase-deficient flies with the mTOR inhibitor rapamycin. Sirolimus 66-75 CREB regulated transcription coactivator 1 Mus musculus 87-93 28496395-8 2017 CONCLUSIONS: Using mouse embryonic fibroblasts, we showed that TSC2-/- KD significantly abrogates lipid biosynthesis and that rapamycin can rescue triglyceride (TG) lipids and we show that SREBP-/- shuts down lipid biosynthesis significantly via mTORC1 signaling pathways. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 246-252 28108221-12 2017 Rapamycin decreased the mTORC1 activity, while increasing the pAkt levels. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 24-30 27692982-0 2017 mTORC1 inhibition with rapamycin exacerbates adipose tissue inflammation in obese mice and dissociates macrophage phenotype from function. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 0-6 28178522-5 2017 Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. Sirolimus 65-74 CREB regulated transcription coactivator 1 Mus musculus 39-45 28202715-4 2017 Using similar paradigms with rapamycin (an mTORC1 inhibitor), we show that preweaning rats (PN18-20) do form a long-term memory of the CS-US interval, and detect a 10-sec versus 30-sec temporal prediction error. Sirolimus 29-38 CREB regulated transcription coactivator 1 Mus musculus 43-49 28057888-8 2017 Re-inactivation of mTORC1 activity via rapamycin may resist hypoxia-induced cell death in TSC1 knockdown lymphocytes. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 19-25 27993682-10 2017 Consistent with a role for mTORC1/S6K1 signaling promoting trastuzumab resistance, all cell lines were sensitive to S6K1 inactivation with significant growth inhibition following treatment with the mTORC1 inhibitor rapamycin. Sirolimus 215-224 CREB regulated transcription coactivator 1 Mus musculus 27-33 27909227-6 2017 In fasted mice, neither basal nor stimulated rates of protein synthesis were affected by castration despite lower phosphorylation of mechanistic target of rapamycin in complex 1 (mTORC1) substrates [p70S6K1 (Thr389) and 4E-BP1 (Ser65)]. Sirolimus 155-164 CREB regulated transcription coactivator 1 Mus musculus 179-185 28067669-8 2017 Rapamycin, an mTORC1 inhibitor, improved muscle relaxation and increased muscle force in HSALR mice without affecting splicing. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 14-20 27993682-10 2017 Consistent with a role for mTORC1/S6K1 signaling promoting trastuzumab resistance, all cell lines were sensitive to S6K1 inactivation with significant growth inhibition following treatment with the mTORC1 inhibitor rapamycin. Sirolimus 215-224 CREB regulated transcription coactivator 1 Mus musculus 198-204 27993682-12 2017 Our results further suggest that trastuzumab resistant breast tumor cells are addicted to mTORC1/S6K1 oncogenic signaling and targeting mTORC1 with rapamycin reverses trastuzumab resistance. Sirolimus 148-157 CREB regulated transcription coactivator 1 Mus musculus 90-96 27993682-12 2017 Our results further suggest that trastuzumab resistant breast tumor cells are addicted to mTORC1/S6K1 oncogenic signaling and targeting mTORC1 with rapamycin reverses trastuzumab resistance. Sirolimus 148-157 CREB regulated transcription coactivator 1 Mus musculus 136-142 28271031-9 2017 Phosphorylation of mTORC1 effector proteins S6 and 4E-BP1 was significantly increased in wild-type mice in response to GLP-2 alone, or when co-administered with protein gavage, and abolished following oral gavage of rapamycin. Sirolimus 216-225 CREB regulated transcription coactivator 1 Mus musculus 19-25 27993979-7 2017 These phenotypes can all be significantly rescued by treatment with the mTORC1 inhibitor rapamycin. Sirolimus 89-98 CREB regulated transcription coactivator 1 Mus musculus 72-78 28746918-12 2017 Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. Sirolimus 71-74 CREB regulated transcription coactivator 1 Mus musculus 208-214 27879318-5 2017 Furthermore, pharmacological inhibition of mTORC1 signaling by rapamycin could also inhibit osteoclast differentiation and osteoclast-specific gene expression. Sirolimus 63-72 CREB regulated transcription coactivator 1 Mus musculus 43-49 27862655-7 2017 Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Sirolimus 164-173 CREB regulated transcription coactivator 1 Mus musculus 185-191 28035937-1 2017 Mammalian target of rapamycin complex 1 (mTORC1), a nutrient sensor and central controller of cell growth and proliferation, is altered in various models of Alzheimer"s disease (AD). Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 41-47 28713484-12 2017 Western blot analysis showed that rapamycin could upregulate ULK1, ATG13 and downregulate mTORC1 and p53 protein expression. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 90-96 27753446-2 2017 Detailed knowledge about the role of the TSC proteins in regulating the activity of the mammalian target of rapamycin complex 1 (mTORC1) underlies this paradigm-shifting progress. Sirolimus 108-117 CREB regulated transcription coactivator 1 Mus musculus 129-135 27754935-8 2017 Rapamycin reversed the activation of mTORC1, attenuated beta cells hypertrophy and abolished the improvement of glucose tolerance. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 37-43 28373901-8 2017 Rapamycin induced phosphorylation of AKT S473 (target of mTORC2) but abolished ribosomal protein S6 phosphorylation (target of mTORC1) after I/R. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 127-133 27933890-1 2016 Recent studies indicate that LRS may act as a leucine sensor for the mTORC1 pathway, potentially providing an alternative strategy to overcome rapamycin resistance in cancer treatments. Sirolimus 143-152 CREB regulated transcription coactivator 1 Mus musculus 69-75 27919264-1 2016 BACKGROUND: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 68-74 27723557-6 2016 The inferior function of statically cultured cardiobundles was rescued by transfer to dynamic conditions, which was accompanied by an increase in mTORC1 activity and decline in AMPK phosphorylation and was blocked by rapamycin. Sirolimus 217-226 CREB regulated transcription coactivator 1 Mus musculus 146-152 27671674-8 2016 PD-L1 attenuation also reduced mTORC1 activity and augmented the antiproliferative effects of the mTORC1 inhibitor rapamycin. Sirolimus 115-124 CREB regulated transcription coactivator 1 Mus musculus 98-104 27797139-4 2016 TSC is caused by the lack of functional Tsc1-Tsc2 complex, which serves as a major cellular inhibitor of mammalian Target of Rapamycin Complex 1 (mTORC1). Sirolimus 125-134 CREB regulated transcription coactivator 1 Mus musculus 146-152 27797139-6 2016 Consequently, mTORC1 inhibitors, such as rapamycin, serve as experimental or already approved drugs for several TSC symptoms. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 14-20 27167250-7 2016 This carbachol-stimulated S6K1 activation was abrogated by LY294002 or the mTORC1 inhibitor rapamycin, supporting the notion that mAChRs mediate S6K1 activation via the PI3K-Akt-mTORC1 pathway. Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 75-81 27167250-7 2016 This carbachol-stimulated S6K1 activation was abrogated by LY294002 or the mTORC1 inhibitor rapamycin, supporting the notion that mAChRs mediate S6K1 activation via the PI3K-Akt-mTORC1 pathway. Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 178-184 27808250-4 2016 Here we observed that rapamycin, which inhibits the nutrient-sensing complex mTORC1, increased ER-mitochondria coupling in HeLa cells to a similar extent as did tunicamycin. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 77-83 27593484-4 2016 Such decreased pro-IL-1beta expression in TSC1 KO macrophages was rescued by reducing mTORC1 activity with rapamycin or deletion of mTOR. Sirolimus 107-116 CREB regulated transcription coactivator 1 Mus musculus 86-92 27332042-12 2016 Treatment with rapamycin selectively blocked mTORC1 activation, NDUFS3 expression, and aPL production both in transaldolase-deficient mice and in lupus-prone mice. Sirolimus 15-24 CREB regulated transcription coactivator 1 Mus musculus 45-51 27822418-6 2016 Pharmacological inhibition of mTORC1 signaling with rapamycin decreased LDHA level and glycolytic capacity of six HCC cell lines. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 30-36 27411383-7 2016 Reduction of GLUT4 protein in sedentary animals upon treatment with rapamycin revealed mTORC1-dependent GLUT4 regulation. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 87-93 27493206-2 2016 The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 157-166 CREB regulated transcription coactivator 1 Mus musculus 178-184 26991739-6 2016 Treatment with 5 mg/kg rapamycin for 3 weeks to inhibit mTORC1 and mTORC2 fully reversed PH in SM22-TSC1(-/-) mice. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 56-62 26991739-7 2016 In chronically hypoxic mice and SM22-5HTT(+) mice exhibiting PH associated with mTORC1 and mTORC2 activation, PH was maximally attenuated by low-dose rapamycin associated with selective mTORC1 inhibition. Sirolimus 150-159 CREB regulated transcription coactivator 1 Mus musculus 80-86 26991739-7 2016 In chronically hypoxic mice and SM22-5HTT(+) mice exhibiting PH associated with mTORC1 and mTORC2 activation, PH was maximally attenuated by low-dose rapamycin associated with selective mTORC1 inhibition. Sirolimus 150-159 CREB regulated transcription coactivator 1 Mus musculus 186-192 27232670-1 2016 The authors have previously demonstrated that a low and intermittent peripheral dose of rapamycin (1 mg/kg three times/week) to rats inhibited mTORC1 signalling, but avoided the hyperlipidemia and diabetes-like syndrome associated with higher doses of rapamycin. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 143-149 26954224-3 2016 In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on ELOVL1 expression and docosahexaenoic acid (DHA, C22:6 n-3) synthesis in bovine mammary epithelial cells (BMECs). Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 84-90 27173058-5 2016 Both increased mTORC1 and decreased mTORC2 activities were reversed by semi-chronic rapamycin treatment. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 15-21 27173058-6 2016 Acute treatment of hippocampal slices from AS mice with rapamycin or an S6K1 inhibitor, PF4708671, improved LTP, restored actin polymerization, and normalized mTORC1 and mTORC2 activity. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 159-165 26872488-4 2016 Notably, blockade of mTORC1 activity by rapamycin treatment prolonged the life span of hyperphosphatemic alpha-Klotho-deficient (Kl(-/-)) mice. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 21-27 27387347-4 2016 These effects were concomitant with constitutive activation of mTORC1 and can be reversed by addition of amino acids or rapamycin, and by the knockdown of the regulatory-associated protein of mTOR, Raptor. Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 63-69 27648364-6 2016 Rapamycin (Sirolimus) is an mTORC1 inhibitor, which inhibits the PI3K/Akt/mTOR signaling pathway, which is commonly altered in prostate cancer. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 28-34 27648364-6 2016 Rapamycin (Sirolimus) is an mTORC1 inhibitor, which inhibits the PI3K/Akt/mTOR signaling pathway, which is commonly altered in prostate cancer. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 28-34 27246732-6 2016 Furthermore, recombinant SEMA3A rescued the attenuation of cell proliferation and glycolytic activity in LLCs after Sema3A knockdown, whereas mTORC1 inhibition by rapamycin completely counteracted this effect. Sirolimus 163-172 CREB regulated transcription coactivator 1 Mus musculus 142-148 27181066-3 2016 For example, central or intra-accumbal injections of the mTORC1 inhibitor rapamycin attenuates several indices of cocaine-seeking including progressive ratio (PR) responding and reinstatement. Sirolimus 74-83 CREB regulated transcription coactivator 1 Mus musculus 57-63 27181066-4 2016 These behavioral effects are associated with decreased mTORC1 activity and synaptic protein translation in the nucleus accumbens (NAC) and point to a possible therapeutic role for rapamycin in the treatment of addiction. Sirolimus 180-189 CREB regulated transcription coactivator 1 Mus musculus 55-61 27181066-11 2016 Thus, systemic administration of rapamycin is as effective at reducing drug seeking behavior and measures of mTORC1 activity compared to direct accumbal application and may therefore represent a possible therapeutic option in the treatment of addiction. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 109-115 27345003-3 2016 A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide-induced alkaline phosphatase activity. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 55-61 27030515-5 2016 Similar effects were observed following oral treatment with the mTORC1 inhibitor, sirolimus. Sirolimus 82-91 CREB regulated transcription coactivator 1 Mus musculus 64-70 27226562-8 2016 Interestingly, inhibition of mTORC1 with rapamycin reduces the abundance of FOXO1 to the levels in T2D. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 29-35 27313209-7 2016 Interestingly, mammalian target of rapamycin complex 1 (mTORC1) signaling was hyperactivated in several tissues from Pip4k2c(-/-) mice and treating Pip4k2c(-/-) mice with rapamycin reduced the inflammatory phenotype, resulting in a decrease in mTORC1 signaling in tissues and a decrease in proinflammatory cytokines in plasma. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 56-62 27313209-7 2016 Interestingly, mammalian target of rapamycin complex 1 (mTORC1) signaling was hyperactivated in several tissues from Pip4k2c(-/-) mice and treating Pip4k2c(-/-) mice with rapamycin reduced the inflammatory phenotype, resulting in a decrease in mTORC1 signaling in tissues and a decrease in proinflammatory cytokines in plasma. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 244-250 27019134-1 2016 Everolimus (EVR) is an orally-administered rapamycin analog that selectively inhibits the mammalian target of rapamycin (mTOR) kinase (mainly mTORC1 and likely mTORC2) and the related signaling pathway. Sirolimus 43-52 CREB regulated transcription coactivator 1 Mus musculus 142-148 27208895-3 2016 mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 44-50 27208895-3 2016 mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Sirolimus 160-169 CREB regulated transcription coactivator 1 Mus musculus 44-50 27208895-5 2016 In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 329-335 27362797-6 2016 Because cells with TSC loss fail to completely inhibit mTORC1 and properly activate autophagy in the absence of amino acids, we sporadically administered the mTORC1 inhibitor rapamycin, which was sufficient to correct the defects seen in cones, further enhancing the efficiency of cone survival mediated by Tsc1 loss. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 158-164 27241713-7 2016 This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 110-116 27338360-4 2016 Rapalogues including sirolimus, everolimus, and temsirolimus exert their effect mainly on mTORC1, whereas their inhibitory effect on mTORC2 is mild. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 90-96 27153561-1 2016 The inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) by chemical inhibitors, such as rapamycin, has demonstrated anti-cancer activity in preclinical and clinical trials. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 65-71 26975583-2 2016 Because TSC tumorigenesis correlates with hyperactivation of mTORC1, current therapies focus on mTORC1 inhibition with rapamycin or its analogs. Sirolimus 119-128 CREB regulated transcription coactivator 1 Mus musculus 96-102 27018708-3 2016 Mice with mTORC1 impairment, either through adipocyte-specific deletion of Raptor or pharmacologic rapamycin treatment, were refractory to the well-known betaAR-dependent increase of uncoupling protein UCP1 expression and expansion of beige/brite adipocytes (so-called browning) in white adipose tissue (WAT). Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 10-16 27078846-2 2016 Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) is the primary alteration underlying TSC tumors. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 60-66 27078846-9 2016 We conclude that downregulation of COX2 exerts a protective effect against hyperactivated mTORC1-mediated tumorigenesis caused by the loss of TSC2, and the combination of rapamycin and celecoxib may be an effective new approach to treating TSC. Sirolimus 171-180 CREB regulated transcription coactivator 1 Mus musculus 90-96 27112200-7 2016 The activation of autophagy including TFEB is likely due to fisetin-mediated mammalian target of rapamycin complex 1 (mTORC1) inhibition, since the phosphorylation levels of p70S6 kinase and 4E-BP1 were decreased in the presence of fisetin. Sirolimus 97-106 CREB regulated transcription coactivator 1 Mus musculus 118-124 26873552-5 2016 Consistently, prenatal treatment with mTORC1 inhibitor rapamycin rescued the phenotype of Depdc5(-/-) embryos. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 38-44 27551516-3 2016 Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 27-33 26858361-7 2016 Accordingly, rapamycin-treated mice are cold intolerant, failing to maintain body temperature and weight when shifted to 4 C. Adipocyte-specific deletion of the mTORC1 subunit Raptor recapitulated the block in beta-adrenergic signaling. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 161-167 26846849-9 2016 Following acute Tsc1 deletion from hepatocytes, Akt phosphorylation, but not IRS1/PI3K association, was rapidly restored by treatment with the mTORC1 inhibitor rapamycin. Sirolimus 160-169 CREB regulated transcription coactivator 1 Mus musculus 143-149 26991235-2 2016 The cause of DA neuronal loss in PD is still unclear; however, accumulating evidence suggests that treatment with certain flavonoids can induce neuroprotective properties, such as activation of mammalian target of rapamycin complex 1 (mTORC1) and anti-inflammatory activities in animal models of PD. Sirolimus 214-223 CREB regulated transcription coactivator 1 Mus musculus 235-241 26816112-2 2016 Central to TSC pathology is hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway, which is a key controller of cell growth. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 93-99 27095138-5 2016 BM cells showed increased phosphorylation of Akt and mTorc1, and extramedullary hematopoiesis was significantly reduced by treating mice with rapamycin in vivo, suggesting that the mTorc1 pathway was activated by loss of Flcn expression in hematopoietic cells in vivo. Sirolimus 142-151 CREB regulated transcription coactivator 1 Mus musculus 181-187 26816112-4 2016 The immunosuppressant, rapamycin, is a specific inhibitor of mTORC1 and has shown promise as a therapeutic agent in TSC as well as in malignancy. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 61-67 27047741-2 2016 In the present study, we examined the in vivo effects of treatment with an mTORC1 inhibitor, rapamycin, on cardiac BCKDH complex activity in mice. Sirolimus 93-102 CREB regulated transcription coactivator 1 Mus musculus 75-81 26844761-10 2016 In this study, we identified many mTORC1-regulated proteins using proteomic analysis by overlapping two different high vs low/no mTORC1 activity comparisons, TSC2(-/-) vs WT MEFs and TSC2(-/-) with/without rapamycin treatment. Sirolimus 206-215 CREB regulated transcription coactivator 1 Mus musculus 34-40 26901106-6 2016 The mTORC1 inhibitor rapamycin diminishes FBP enrichment in liver tumors after hydrodynamic gene delivery of AKT plasmids. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 26854565-6 2016 Using a large-scale, unbiased quantitative proteomic platform, we comprehensively characterized the rapamycin-sensitive secretome in TSC2(-/-) mouse embryonic fibroblasts, and identified IGFBP5 as a secreted, mTORC1 downstream effector protein. Sirolimus 100-109 CREB regulated transcription coactivator 1 Mus musculus 209-215 26872016-4 2016 Moreover, several recent clinical trials showed that the mTORC1 inhibitors rapamycin and rapalog only reduce the capacity for cell proliferation without promoting cell death, consistent with the concept that rapamycin is cytostatic and reduces disease progression but is not cytotoxic. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 57-63 26872016-6 2016 Here, we report that rapamycin treatment promotes a compensatory increase in transglutaminase 2 (TGM2) levels in mTORC1-driven tumors. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 113-119 26872016-7 2016 TGM2 inhibition potently sensitizes mTORC1-hyperactive cancer cells to rapamycin treatment, and a rapamycin-induced autophagy blockade inhibits the compensatory TGM2 upregulation. Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 36-42 26872016-7 2016 TGM2 inhibition potently sensitizes mTORC1-hyperactive cancer cells to rapamycin treatment, and a rapamycin-induced autophagy blockade inhibits the compensatory TGM2 upregulation. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 36-42 26878791-5 2016 Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 130-136 26655465-1 2016 Expression of hypoxia-inducible factor 1a (HIF1a) is increased under several pathological conditions such as hyperactive mechanistic target of rapamycin complex 1 (mTORC1) in tuberous sclerosis complex (TSC). Sirolimus 143-152 CREB regulated transcription coactivator 1 Mus musculus 164-170 27042678-6 2016 RESULTS: Kainate-induced seizures caused acute activation of mTORC1 activity, which was prevented by the mTORC1 inhibitor, rapamycin. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 61-67 27042678-6 2016 RESULTS: Kainate-induced seizures caused acute activation of mTORC1 activity, which was prevented by the mTORC1 inhibitor, rapamycin. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 105-111 26702100-7 2016 Importantly, inhibition of mTORC1 signaling by rapamycin treatment aggravated the neurodegenerative phenotype in a TDP-43-depleted Drosophila model, whereas activation of mTORC1 signaling by PA treatment ameliorated the neurodegenerative phenotype. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 27-33 26923592-2 2016 We show that the amino acid sensing of mechanistic target of rapamycin complex 1 (mTORC1) is dysregulated in cells deficient in presenilin, a protein associated with AD. Sirolimus 61-70 CREB regulated transcription coactivator 1 Mus musculus 82-88 26698023-9 2016 Rapamycin (which primarily inhibits mTORC1), ATP-competitive, dual mTORC1/mTORC2 inhibitors and upstream regulators of the mTOR pathway are being developed to treat autoimmune, hyperproliferative and degenerative diseases. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 36-42 26463117-3 2016 While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 100-106 26463117-3 2016 While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. Sirolimus 139-148 CREB regulated transcription coactivator 1 Mus musculus 100-106 26463117-3 2016 While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. Sirolimus 139-148 CREB regulated transcription coactivator 1 Mus musculus 100-106 26463117-4 2016 We hypothesized that different rapamycin dosing schedules or the use of FDA-approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 215-221 26419955-0 2016 Analysis of Proteins That Rapidly Change Upon Mechanistic/Mammalian Target of Rapamycin Complex 1 (mTORC1) Repression Identifies Parkinson Protein 7 (PARK7) as a Novel Protein Aberrantly Expressed in Tuberous Sclerosis Complex (TSC). Sirolimus 78-87 CREB regulated transcription coactivator 1 Mus musculus 99-105 26419955-8 2016 We provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin has little effect globally, yet leads to a significant remodeling of synaptic proteins, in particular those proteins that reside in the postsynaptic density. Sirolimus 74-83 CREB regulated transcription coactivator 1 Mus musculus 47-53 26795955-3 2016 Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium. Sirolimus 95-104 CREB regulated transcription coactivator 1 Mus musculus 122-128 26795955-4 2016 The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 26795955-4 2016 The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 189-195 25867072-3 2016 Rapamycin analogs Everolimus and Temsirolimus are non-ATP-competitive mTORC1 inhibitors, and suppress proliferation and tumor angiogenesis and invasion. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 70-76 27047741-5 2016 Rapamycin treatment fully inhibited mTORC1 activity, measured by the phosphorylation state of ribosomal protein S6 kinase 1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 36-42 26565025-8 2015 Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-beta1. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 14-20 26563881-2 2016 mTORC1, consisting of mTOR, raptor, and mLST8 (GbetaL), is sensitive to rapamycin and thought to control autonomous cell growth in response to nutrient availability and growth factors. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 0-6 26563881-6 2016 However, the effectiveness of rapamycin as single-agent therapy is suppressed, in part, by the numerous strong mTORC1-dependent negative feedback loops. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 111-117 26636543-2 2015 Here we studied the role of mTOR-dependent autophagy in implementating the antiprolifrative effect of mTORC1-specific inhibitor rapamycin and ATP-competitive mTOR kinase inhibitor pp242. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 102-108 26563389-7 2016 Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 37-43 27468872-3 2016 Although several evidences suggest that hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is crucial for these tumors, modulation of other metabolic pathways might affect tumor growth and progression. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 105-111 26566676-7 2015 Akt-mediated downregulation of Mfn2 was via the mTORC1 pathway because this downregulation was blocked by rapamycin, and overexpression of wild-type, but not kinase-dead mTOR, caused Mfn2 downregulation. Sirolimus 106-115 CREB regulated transcription coactivator 1 Mus musculus 48-54 26130148-5 2015 On the other hand, the allosteric inhibitor rapamycin induces eIF2alphaS51P through pathways that are independent of mTORC1 inactivation. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 117-123 26449264-2 2015 This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Sirolimus 168-177 CREB regulated transcription coactivator 1 Mus musculus 200-206 26693177-2 2015 The TSC1 and TSC2 proteins form a complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 97-103 25844891-8 2015 Therefore, the combination of rapamycin and resveratrol may be an effective clinical strategy for treatment of LAM and other diseases with mTORC1 hyperactivation. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 139-145 26002629-0 2015 Rapamycin prevents cadmium-induced neuronal cell death via targeting both mTORC1 and mTORC2 pathways. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 74-80 26002629-9 2015 The findings indicate that rapamycin prevents Cd-induced neuronal cell death via suppressing both mTORC1 and mTORC2 pathways. Sirolimus 27-36 CREB regulated transcription coactivator 1 Mus musculus 98-104 26027949-11 2015 Inhibition of mTORC1 activity by rapamycin improved the behavioral and immunological deficits of CMA mice. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 14-20 26402468-8 2015 Synergy was observed when buparlisib was combined with the IGF1R inhibitor NVP-AEW541 and the mTORC1 inhibitor rapamycin. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 94-100 26241748-6 2015 The mTORC1-specific inhibitor, rapamycin, restored these in vitro and in vivo phenotypic changes. Sirolimus 31-40 CREB regulated transcription coactivator 1 Mus musculus 4-10 26306297-9 2015 Rapamycin treatment specifically inhibited LV mTORC1 without altering mTORC2 activity at 8 weeks. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 46-52 26306297-11 2015 CONCLUSION: Rapamycin slows hypertrophy in LV VO by inhibiting early activation of mTORC1 without modulating mTORC2. Sirolimus 12-21 CREB regulated transcription coactivator 1 Mus musculus 83-89 26163589-4 2015 Persistent Ag exposure results in prolonged activation of the AKT-mTORC1 pathway in Ag-specific CD8 T cells, favoring their development into effector memory T cells at the expense of central memory T cells, and inhibition of mTORC1 by rapamycin largely corrects the impairment by promoting central memory T cell development. Sirolimus 235-244 CREB regulated transcription coactivator 1 Mus musculus 225-231 26041819-5 2015 mTORC1 inhibition with rapamycin partially ameliorated renal disease in B6.Pdss2(kd/kd) mice with complexes I-III/II-III deficiencies, improved viability and mitochondrial physiology in gas-1(fc21) nematodes with complex I deficiency, and rescued viability across a variety of RC-inhibited human cells. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 0-6 25936601-3 2015 In the present study, we examined the effect of rapamycin, an mTORC1 inhibitor and an inducer of autophagy, on recovery from spinal cord injury. Sirolimus 48-57 CREB regulated transcription coactivator 1 Mus musculus 62-68 26032503-6 2015 In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 29-35 26200935-3 2015 The concern with the monotherapy use of mTORC1 inhibitors, such as rapamycin, is that they cause upregulation of autophagy, a cell survival mechanism, and suppress the negative feedback loop to the oncogene Akt. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 40-46 26170311-3 2015 Rapamycin is an allosteric inhibitor of mTOR that selectively inhibits mTORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 71-77 25997742-4 2015 Lysosomes are dynamic organelles that integrate several degradative pathways and regulate the activity of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 147-153 26051878-8 2015 Inhibitors of mTORC1, such as rapamycin, effectively suppress the symptoms of TSC. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 14-20 26002468-3 2015 We showed that autophagy was induced in an mTORC1-dependent way and played a protective role against PA-induced apoptosis, which was verified by pretreatment with 3-methyladenine (3MA) and rapamycin. Sirolimus 189-198 CREB regulated transcription coactivator 1 Mus musculus 43-49 25836987-9 2015 Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 264-270 26176608-5 2015 In this study, by employing automated spectrophotometry, we found the level of glucose uptake was decreased in non-small-cell lung carcinoma (NSCLC) A549, PC-9 and SK-MES-1 cells treated with rapamycin or siRNA against Raptor, indicating that the inhibition of mTORC1 attenuated glycolytic metabolism in NSCLC cells. Sirolimus 192-201 CREB regulated transcription coactivator 1 Mus musculus 261-267 25703582-4 2015 Several recent reports showed that rapamycin, an inhibitor of mTORC1, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORC1 overactivity playing an important pathogenic role. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 62-68 25703582-4 2015 Several recent reports showed that rapamycin, an inhibitor of mTORC1, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORC1 overactivity playing an important pathogenic role. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 202-208 26219339-4 2015 Our previous work demonstrated aberrant activation of mTORC1 signaling that led to ongoing clinical trials with rapamycin analogs for NF2 and sporadic meningioma patients. Sirolimus 112-121 CREB regulated transcription coactivator 1 Mus musculus 54-60 25813876-6 2015 The mTOR complex (C)1/S6K1 blocker rapamycin inhibited the phosphorylation of IRS-1 at Ser636 in cells overexpressing alpha-Syn, suggesting that mTORC1/S6K1 activation by alpha-Syn causes feedback inhibition of insulin signaling via suppression of IRS-1 function. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 145-151 26086828-7 2015 Similar effects were obtained in cells in which mTORC1 was inhibited by rapamycin. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 48-54 25911189-7 2015 Rapamycin treatment restored phosphorylation of STAT3 and enhanced AKT phosphorylation (target of mTORC2), but significantly reduced ribosomal protein S6 phosphorylation (target of mTORC1) in the diabetic heart. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 181-187 26083118-7 2015 The effect of Orz on adipocyte differentiation was dependent on mTORC1 activity because rapamycin blocks cell differentiation in Orz-treated cells. Sirolimus 88-97 CREB regulated transcription coactivator 1 Mus musculus 64-70 25794661-5 2015 Rapamycin, an inhibitor of mTORC1 (mTOR complex 1) did not elicit apoptosis in lymphoma cells; however, the combination of rapamycin with exogenous TGF-beta1 induced apoptosis and restored TGF-beta1 dependent apoptotic machinery in several lymphoma cell lines with reduced TGF-beta sensitivity in vitro. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 27-33 25988388-5 2015 The suppression of HIF-1alpha and VEGF by rapamycin was associated with dephosphorylation of mTOR and the downstream effector ribosomal protein S6 kinase (P70S6K) and 4E-binding protein-1 (4E-BP1) of mTORC1. Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 200-206 26060906-8 2015 Mutations in the TSC1 and TSC2 genes that cause tuberous sclerosis lead to hyperactivation of signaling via the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 132-141 CREB regulated transcription coactivator 1 Mus musculus 153-159 25961827-0 2015 AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 96-102 25721400-5 2015 Feeding the mice with a diet supplemented with rapamycin prevented the enlargement of the heart and spleen, suggesting that mTORC1 is the mediator of these effects. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 124-130 25721400-9 2015 These observations suggest that the anabolic effect of mTORC1 activation at the organ level by BCAAs and inhibition by rapamycin are complex phenomenon and tissue-specific. Sirolimus 119-128 CREB regulated transcription coactivator 1 Mus musculus 55-61 25721400-10 2015 In addition, it suggests that rapamycin can be used to counter hypertrophy of the organs when activation of mTORC1 is the underlying cause. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 108-114 25855786-3 2015 Although rapamycin analogues, allosteric inhibitors that target only the mTORC1 complex, have shown some clinical activity, it is hypothesized that mTOR kinase inhibitors, blocking both mTORC1 and mTORC2 signaling, will have expanded therapeutic potential. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 73-79 25855786-3 2015 Although rapamycin analogues, allosteric inhibitors that target only the mTORC1 complex, have shown some clinical activity, it is hypothesized that mTOR kinase inhibitors, blocking both mTORC1 and mTORC2 signaling, will have expanded therapeutic potential. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 186-192 25942007-6 2015 Inhibition of PI3K with LY294002 and wortmannin, and of mTORC1 with rapamycin decreased flagellin-induced TNF-alpha and IL-6 expression and cell proliferation. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 56-62 25659819-6 2015 Data are provided demonstrating that G1 cell cycle arrest induced by rapamycin is due to up-regulation of TGF-beta signaling and down-regulation of Rb phosphorylation via phosphorylation of the mTORC1 substrates S6K and 4E-BP1 respectively. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 194-200 25880554-9 2015 Use of specific estrogen receptor (ER)alpha- and ERbeta-agonists indicated involvement of both estrogen receptors (ER) in rapamycin effects on mTORC1 and mTORC2. Sirolimus 122-131 CREB regulated transcription coactivator 1 Mus musculus 143-149 25738543-3 2015 The protein complex TSC1/2 has been reported to have an inhibitory function on mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 120-126 25866192-3 2015 Here we show that gene expression for several myogenic transcription factors including Myf5, Myog and Mef2c but not MyoD and myosin heavy chain isoforms decrease when C2C12 cells are treated with rapamycin, supporting a role for mTORC1 pathway during muscle development. Sirolimus 196-205 CREB regulated transcription coactivator 1 Mus musculus 229-235 25537496-4 2015 While compounds used to study mTOR signaling, such as rapamycin and related analogs, primarily inhibit mTORC1, prolonged exposure can also disrupt mTORC2 function, confounding interpretation of inhibitor studies. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 103-109 25652038-2 2015 While rapamycin acutely and directly inhibits mTORC1, only chronic administration of rapamycin can inhibit mTORC2 in some, but not all, cell lines or tissues. Sirolimus 6-15 CREB regulated transcription coactivator 1 Mus musculus 46-52 25652038-6 2015 Further reduction of FKBP12 in cell lines with already low FKBP12 levels completely blocks mTORC1 inhibition by rapamycin, indicating that relative FKBP12 levels are critical for both mTORC1 and mTORC2 inhibition, but at different levels. Sirolimus 112-121 CREB regulated transcription coactivator 1 Mus musculus 91-97 25383520-8 2015 Importantly, treatment of established APC-deficient adenomas with rapamycin (which can target eEF2 through the mTORC1-S6K-eEF2K axis) causes tumour cells to undergo growth arrest and differentiation. Sirolimus 66-75 CREB regulated transcription coactivator 1 Mus musculus 111-117 25762619-5 2015 Also, PP242, an mTORC1/2 kinase inhibitor, inhibited cell adhesion more potently than rapamycin (mTORC1 inhibitor). Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 97-103 25466898-7 2015 Inhibition of mTOR complex 1 (mTORC1) by rapamycin [drug concentration causing 50% inhibition (IC50) = 5 nM] and mTORC1/mTORC2 by Torin2 (IC50 = 6 nM), or by knocking down key mTORC1/2 components, Raptor and Rictor, respectively, decreased directional cell migration toward CXCL12. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 30-36 25466898-9 2015 It is surprising that mTORC1 disruption by Raptor knockdown was sufficient to reduce tumor growth by 60% and spontaneous metastasis by 72%, which were nearly abolished by rapamycin. Sirolimus 171-180 CREB regulated transcription coactivator 1 Mus musculus 22-28 25336146-3 2015 In the present study we investigated the effects of combination therapy of rapamycin (an allosteric mTORC1 inhibitor) together with resveratrol (a phytoestrogen that inhibits autophagy). Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 100-106 25738366-10 2015 Our findings suggest that rapamycin inhibits mSin1 phosphorylation, which is independent of mTORC1 and mTORC2, but is possibly dependent on a new mTOR complex, which at least contains mTOR and mLST8. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 92-98 25613864-1 2015 The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 229-238 CREB regulated transcription coactivator 1 Mus musculus 250-256 25613864-5 2015 mTORC1 is a master regulator of growth processes, and its activity can be reduced by withdrawal of growth factors, decreased energy availability, and by the immunosuppressant rapamycin. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 0-6 24632604-9 2015 Long-term treatment with rapamycin reduced both Akt and mTORC1 activity in normal kidney tissues and blocked the development of all types of renal lesions. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 56-62 25512609-2 2015 In mammals, LD synthesis is inhibited by rapamycin, a known inhibitor of the mTORC1 pathway. Sirolimus 41-50 CREB regulated transcription coactivator 1 Mus musculus 77-83 25512609-9 2015 The TORC1-controlled transcriptional activators Gln3p, Gat1p, Rtg1p, and Rtg3p, but not Msn2p and Msn4p, were required for full induction of LDs by rapamycin. Sirolimus 148-157 CREB regulated transcription coactivator 1 Mus musculus 4-9 25774780-8 2015 Interestingly, the acute orexigenic effect of the mTORC1 inhibitor rapamycin was preserved in HF-fed mice, supporting the assertion that HF-induced increase in baseline cmNTS mTORC1 activity underlies the defect in L-leucine sensing. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 50-56 25774780-8 2015 Interestingly, the acute orexigenic effect of the mTORC1 inhibitor rapamycin was preserved in HF-fed mice, supporting the assertion that HF-induced increase in baseline cmNTS mTORC1 activity underlies the defect in L-leucine sensing. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 175-181 25761126-3 2015 Inputs of the model include intrinsic AMPK kinase activity, which is taken as an adjustable surrogate parameter for cellular energy level or AMP:ATP ratio, and rapamycin dose, which controls MTORC1 activity. Sirolimus 160-169 CREB regulated transcription coactivator 1 Mus musculus 191-197 25590801-7 2015 Inhibition of mTORC1 by rapamycin restores Akt activity in eIF2alphaP-deficient cells but renders them highly susceptible to Akt-mediated death by oxidative stress. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 25524627-1 2015 The mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals from growth factors, nutrients, and cellular energy status to control a wide range of metabolic processes, including mRNA biogenesis; protein, nucleotide, and lipid synthesis; and autophagy. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 25524627-3 2015 Recent studies have shown that the mTORC1 inhibitor rapamycin and its analogs generally suppress proliferation rather than induce apoptosis. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 35-41 26112996-3 2015 METHODS: We stimulated trout primary hepatocytes with different AA levels and employed acute administration of rapamycin to inhibit mTORC1 activation. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 132-138 25442674-2 2015 mTORC1 function is tightly regulated by PI3-K/Akt and is sensitive to rapamycin. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 0-6 24925055-3 2015 In this study, we sought evidence of mechanistic target of rapamycin complex 1 (mTORC1) activation in fibrolamellar carcinoma, based on anecdotal reports of tumor response to rapamycin analogs. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 80-86 25185584-2 2015 The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 93-99 25185584-3 2015 Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 14-20 25185584-5 2015 Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. Sirolimus 133-142 CREB regulated transcription coactivator 1 Mus musculus 182-188 25476905-5 2014 Rapamycin (sirolimus) is a known specific inhibitor of mTORC1, whereas S-trans,trans-farnesylthiosalicylic acid (FTS; salirasib) has been shown to inhibit Rheb. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 55-61 25239638-2 2015 Sirolimus and everolimus indirectly bind and inhibit mTORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 53-59 26339682-4 2015 We here observed the effect of intrathecal infusion of rapamycin, a specific mTORC1 inhibitor, on morphine-induced tolerance and hyperalgesia in a neuropathic pain model in rats induced by the fifth lumbar spinal nerve ligation (SNL). Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 77-83 25453101-10 2014 On the other hand, rapamycin treatment leads to transient appearance of monomeric mTORC1 before complete disruption of the mTOR-raptor interaction, whereas mTORC2 stoichiometry is unaffected. Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 82-88 25628925-4 2015 In the present study, we describe that AZD2014, a small molecular ATP-competitive inhibitor of mTOR, was a highly potent inhibitor of mTORC1 and mTORC2 in human HCC cells, which led to a more thorough inhibition of mTORC1 than rapamycin, and the inhibition of mTORC2 prevented the feedback activation of AKT signaling. Sirolimus 227-236 CREB regulated transcription coactivator 1 Mus musculus 134-140 25628925-4 2015 In the present study, we describe that AZD2014, a small molecular ATP-competitive inhibitor of mTOR, was a highly potent inhibitor of mTORC1 and mTORC2 in human HCC cells, which led to a more thorough inhibition of mTORC1 than rapamycin, and the inhibition of mTORC2 prevented the feedback activation of AKT signaling. Sirolimus 227-236 CREB regulated transcription coactivator 1 Mus musculus 215-221 25514416-8 2014 Incubation of cells with rapamycin, a known inhibitor of mTOR kinase activity, increased the total Edc4 protein expression but at the same time decreased the Edc4 interaction with mTORC1. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 180-186 25096520-8 2014 On the other hand, the mTORC1 inhibitor rapamycin prevented increases in phosphorylated S6, protein synthesis and myotube diameter. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 23-29 25476905-5 2014 Rapamycin (sirolimus) is a known specific inhibitor of mTORC1, whereas S-trans,trans-farnesylthiosalicylic acid (FTS; salirasib) has been shown to inhibit Rheb. Sirolimus 11-20 CREB regulated transcription coactivator 1 Mus musculus 55-61 25243405-11 2014 Finally, we found that the effects of ICK or MOK knockdown on cilium length and IFT are suppressed by rapamycin treatment, suggesting that these effects require the mTORC1 pathway. Sirolimus 102-111 CREB regulated transcription coactivator 1 Mus musculus 165-171 24825564-6 2014 Pretreatment with the mTORC1 inhibitor rapamycin not only alleviated pulmonary arterial pressure and pulmonary arteriolar remodeling but also suppressed hypoxia-induced mTORC1 and Notch3 activation. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 22-28 24825564-6 2014 Pretreatment with the mTORC1 inhibitor rapamycin not only alleviated pulmonary arterial pressure and pulmonary arteriolar remodeling but also suppressed hypoxia-induced mTORC1 and Notch3 activation. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 169-175 25278019-4 2014 This orexin/GPCR-stimulated mTOR activation is sensitive to rapamycin, an inhibitor of mTOR complex 1 (mTORC1) but is independent of two well known mTORC1 activators, Erk and Akt. Sirolimus 60-69 CREB regulated transcription coactivator 1 Mus musculus 103-109 24114993-5 2014 Targeting mTORC1 with rapamycin effectively inhibited TPA-induced epidermal hyperplasia and hyperproliferation as well as tumor promotion in a dose-dependent manner in both wild-type and BK5.Akt(WT) mice. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 10-16 25174408-9 2014 Finally, rapamycin, an mTORC1 inhibitor, was used to treat the CAC model. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 23-29 25075795-9 2014 Moreover, inhibition of mTORC1 by rapamycin (2 mg/kg, intraperitoneally) enhanced the anticancer activity of oridonin in mice xenograft models. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 24-30 24865460-6 2014 Inhibition of mTORC1 by rapamycin restored sensitivity of adrenocortical cells to apoptosis in AdKO but not in wild-type mice. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 25193863-3 2014 We provide evidence that mTORC1 inhibition by rapamycin results in engagement of a negative feedback regulatory loop in malignant medulloblastoma cells, involving phosphorylation of the eukaryotic translation-initiation factor eIF4E. Sirolimus 46-55 CREB regulated transcription coactivator 1 Mus musculus 25-31 24847003-2 2014 In human ADPKD studies, sirolimus, a mammalian target of rapamycin complex 1 (mTORC1) inhibitor, had little therapeutic effect. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 78-84 24847003-3 2014 While sirolimus robustly inhibits mTORC1, it has a minimal effect on mTOR complex 2 (mTORC2). Sirolimus 6-15 CREB regulated transcription coactivator 1 Mus musculus 34-40 25053409-2 2014 In contrast, low doses of rapamycin (10 mug/kg) increase mTORC1 activity and protein synthesis in skeletal muscle. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 57-63 24631968-5 2014 AMN082 administered 60 min before the test increased the levels of pmTOR and pp70S6K, and the mTORC1 antagonist rapamycin reversed AMN082-induced changes in the forced swim test (FST) in rats. Sirolimus 112-121 CREB regulated transcription coactivator 1 Mus musculus 94-100 25016184-8 2014 We reversed the anti-inflammatory phenotype of Rtp801(-/-) mice with the mTORC1 inhibitor, rapamycin, reassuring against mTORC1-independent effects of Rtp801. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 73-79 25016184-8 2014 We reversed the anti-inflammatory phenotype of Rtp801(-/-) mice with the mTORC1 inhibitor, rapamycin, reassuring against mTORC1-independent effects of Rtp801. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 121-127 24962700-3 2014 Although mTOR was originally discovered as a target protein of rapamycin, a natural macrolide immunosuppressant, rapamycin mainly inhibits the kinase activity of mTORC1, whereas mTORC2 is affected to a much lesser extent. Sirolimus 63-72 CREB regulated transcription coactivator 1 Mus musculus 162-168 24973821-6 2014 The mTORC1 inhibitor rapamycin inhibited NK cell cytotoxicity both in mice and humans; this probably contributes to the immunosuppressive activity of this drug in different clinical settings. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 25084011-8 2014 In addition, we revealed that treatment with rapamycin (an mTORC1 inhibitor) aggravated the deficiency in B cell development in the PB and BM. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 59-65 24599401-2 2014 TSC1/2 protein complex negatively regulates the mammalian target of rapamycin complex 1 (mTORC1) a master regulator of protein synthesis, cell growth and autophagy. Sirolimus 68-77 CREB regulated transcription coactivator 1 Mus musculus 89-95 24910242-5 2014 Notably, rapamycin treatment or hepatocyte-specific ablation of the specific mTORC1 subunit Raptor resulted in elevated interleukin-6 (IL-6) production, activation of signal transducer and activator of transcription 3 (STAT3), and enhanced HCC development, despite a transient reduction in hepatosteatosis. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 77-83 25128827-7 2014 Moreover, PGE2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Sirolimus 150-159 CREB regulated transcription coactivator 1 Mus musculus 140-146 25058027-5 2014 In this study, we used a Cox2 inhibitor, celecoxib, and an mTORC1 inhibitor, rapamycin, in mouse models of EMC and in human EMC cell lines to explore the interactive roles of Cox2 and mTORC1 signaling. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 59-65 25711103-4 2014 It exists in two mTOR protein complexes mTORC1 and mTORC2 with various sensitivity to the inhibitory effect of rapamycin. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 40-46 24650522-4 2014 Utilizing both rapamycin to inhibit mTORC1 activity and shRNA to knock down Rheb, we demonstrated that the decrease in Akt Ser473 phosphorylation stimulated by insulin after C2-ceramide incubation can be prevented. Sirolimus 15-24 CREB regulated transcription coactivator 1 Mus musculus 36-42 24311731-7 2014 The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Sirolimus 21-30 CREB regulated transcription coactivator 1 Mus musculus 4-10 25161886-2 2014 A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. Sirolimus 177-186 CREB regulated transcription coactivator 1 Mus musculus 160-166 24469593-7 2014 Rapamycin reduced drug seeking in signaled non-drug-available periods, PR responding, and cue-induced reinstatement, with these effects linked to reduced mTORC1 activity, total CAMKIIalpha, and GluA1 AMPAR levels in the NACsh. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 154-160 24889507-2 2014 Tsc1 and Tsc2 proteins form a complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) signalling through Rheb-GTPase. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 93-99 24615339-4 2014 Interestingly, REDD1 induction was impaired in glucocorticoid-resistant ALL cells and inhibition of mTORC1 using rapamycin restored glucocorticoid sensitivity. Sirolimus 113-122 CREB regulated transcription coactivator 1 Mus musculus 100-106 23584478-2 2014 Rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1), was known to inhibit protein synthesis. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 68-74 24691032-0 2014 Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin. Sirolimus 127-136 CREB regulated transcription coactivator 1 Mus musculus 14-20 24691032-12 2014 We conclude that activation of mTORC1 signaling and protein synthesis in human muscle following BFR exercise is inhibited in the presence of rapamycin. Sirolimus 141-150 CREB regulated transcription coactivator 1 Mus musculus 31-37 24683191-5 2014 Rapamycin inhibited mTORC1 and enhanced mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 20-26 24569994-7 2014 Moreover, treatment of fibroblasts over-expressing tTG with PP2, or with inhibitors that inactivate components of the PI3-kinase pathway, including PI3-kinase (LY294002) and mTORC1 (rapamycin), ablated the tTG-promoted survival of the cells. Sirolimus 182-191 CREB regulated transcription coactivator 1 Mus musculus 174-180 24580843-6 2014 These results suggest that everolimus is more effective than sirolimus at antagonizing both mTORC1 and mTORC2, the latter of which is critical in endothelial cell functional changes leading to TV in solid organ transplantation after HLA I crosslinking. Sirolimus 61-70 CREB regulated transcription coactivator 1 Mus musculus 92-98 24414536-2 2014 Recently, merlin, the NF2 tumor suppressor, has been identified as a novel negative regulator of mammalian target of rapamycin complex 1 (mTORC1); functional loss of merlin was shown to result in elevated mTORC1 signaling in NF2-related tumors. Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 138-144 24414536-2 2014 Recently, merlin, the NF2 tumor suppressor, has been identified as a novel negative regulator of mammalian target of rapamycin complex 1 (mTORC1); functional loss of merlin was shown to result in elevated mTORC1 signaling in NF2-related tumors. Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 205-211 24414536-5 2014 RESULTS: We found that treatment with the mTORC1 inhibitor rapamycin reduced the severity of NF2-related Schwann cell tumorigenesis without significant toxicity. Sirolimus 59-68 CREB regulated transcription coactivator 1 Mus musculus 42-48 24591659-3 2014 Pivotal clinical trials have demonstrated that inhibition of mTORC1 with sirolimus can induce a partial response of TSC-associated tumours and decrease the rate of lung function decline in females with LAM. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 61-67 24515103-7 2014 Western blot and morphological analyses indicated that TGF-beta signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. Sirolimus 211-220 CREB regulated transcription coactivator 1 Mus musculus 148-154 24515103-7 2014 Western blot and morphological analyses indicated that TGF-beta signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. Sirolimus 211-220 CREB regulated transcription coactivator 1 Mus musculus 185-191 24445976-1 2014 OBJECTIVES: Erlotinib and Rapamycin are both in clinical use and experimental inhibition of their respective molecular targets, EGFR and mTORC1, has improved recovery from spinal cord injury. Sirolimus 26-35 CREB regulated transcription coactivator 1 Mus musculus 137-143 24445976-10 2014 In vitro studies confirmed that Erlotinib and Rapamycin both inhibit the EGFR-mTORC1 signaling pathway. Sirolimus 46-55 CREB regulated transcription coactivator 1 Mus musculus 78-84 24570486-4 2014 We found that at later stages after denervation of fast-twitch muscle, activation of mTORC1 contributed to atrophy and that denervation-induced atrophy was mitigated by inhibition of mTORC1 with rapamycin. Sirolimus 195-204 CREB regulated transcription coactivator 1 Mus musculus 183-189 24570486-6 2014 Rapamycin treatment of mice restored Akt activity, suggesting that the denervation-induced increase in mTORC1 activity was producing feedback inhibition of Akt. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 103-109 24226526-2 2014 Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC), leading to one of the clearest therapeutic opportunities to target mTOR with rapamycin and its analogs ("rapalogs"), which effectively inhibit mTOR complex 1 (mTORC1) by an allosteric mechanism. Sirolimus 181-190 CREB regulated transcription coactivator 1 Mus musculus 263-269 24196830-9 2014 Combinations of metformin and rapamycin were more effective at blocking epidermal mTORC1 signaling induced by TPA consistent with the greater inhibitory effect on skin tumor promotion. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 82-88 24273170-9 2014 Inhibition of phosphatidylinositol 3-kinase with wortmannin or mTORC1 with rapamycin effectively inhibits the increased assembly observed upon cluster disruption. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 63-69 24481314-4 2014 Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/- mice by 50%. Sirolimus 124-133 CREB regulated transcription coactivator 1 Mus musculus 107-113 24018642-6 2014 Combination of rapamycin with sunitinib resulted in enhanced cell cycle arrest in G1 phase, which was accompanied with enhanced suppression of mTOR signaling and disruption of the negative feedback loop that activate AKT upon mTORC1 inhibition. Sirolimus 15-24 CREB regulated transcription coactivator 1 Mus musculus 226-232 26097864-5 2014 We have recently reported that selective inhibition of mTORC1 by rapamycin or its analogs in medulloblastoma cells results in phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) on serine-209, an event known to be associated with induction of protein translation and cell transformation. Sirolimus 65-74 CREB regulated transcription coactivator 1 Mus musculus 55-61 24101601-5 2014 Inhibition of mTORC1/S6 kinase signaling by rapamycin induced colocalization of mitochondria with autophagosomes, and resulted in a striking progressive decrease in levels of the G11778A mutation and partial restoration of ATP levels. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 14-20 24401275-3 2014 Targeted depletion of MAPK-interacting Ser/Thr kinase 1 (MNK1) sensitizes glioma cells to the mTORC1 inhibitor rapamycin through an indistinct mechanism. Sirolimus 111-120 CREB regulated transcription coactivator 1 Mus musculus 94-100 24404143-0 2014 Rapamycin ameliorates inflammation and fibrosis in the early phase of cirrhotic portal hypertension in rats through inhibition of mTORC1 but not mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 130-136 24404143-11 2014 Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Sirolimus 89-98 CREB regulated transcription coactivator 1 Mus musculus 45-51 24407515-7 2014 In contrast, MCF-7/GSK-3beta(KD) cells displayed an elevated sensitivity to the mTORC1 blocker rapamycin compared with MCF-7/GSK-3beta(WT) or MCF-7/GSK-3beta(A9) cells, while no differences between the 3 cell types were observed upon treatment with a MEK inhibitor by itself. Sirolimus 95-104 CREB regulated transcription coactivator 1 Mus musculus 80-86 24304514-2 2014 The concern with the use of mTORC1 inhibitors, such as rapamycin or its analogs (rapalogs), is that they cause upregulation of autophagy and suppress the negative feedback loop to Akt, which promotes cell survival, causing the therapy to be only partially effective, and relapse occurs upon cessation of treatment. Sirolimus 55-64 CREB regulated transcription coactivator 1 Mus musculus 28-34 24304514-7 2014 Thus, the addition of resveratrol to rapamycin treatment may be a promising option for selective and targeted therapy for diseases with TSC loss and mTORC1 hyperactivation. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 149-155 24407515-11 2014 Taken together, these results demonstrate that introduction of GSK-3beta(KD) into MCF-7 breast cancer cells promotes resistance to doxorubicin and tamoxifen, but sensitizes the cells to mTORC1 blockade by rapamycin. Sirolimus 205-214 CREB regulated transcription coactivator 1 Mus musculus 186-192 24123525-6 2013 Pharmacological inhibition of mTORC1 activity in vivo by rapamycin treatment leads to a marked, but partial, suppression of primordial follicle activation. Sirolimus 57-66 CREB regulated transcription coactivator 1 Mus musculus 30-36 24108520-6 2013 Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 145-151 24292708-4 2014 Here, we tested the hypothesis that aptamer-targeted siRNA inhibition of mTOR complex 1 (mTORC1) function in CD8(+) T cells can enhance their differentiation into memory T cells and potentiate antitumor immunity more effectively than the pharmacologic inhibitor rapamycin. Sirolimus 262-271 CREB regulated transcription coactivator 1 Mus musculus 89-95 23994018-4 2013 Rapamycin, an inhibitor of mTORC1, suppressed ghrelin-induced phosphorylation of hypothalamic S6K1 and increased food intake and insulin in rats. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 27-33 24337840-5 2013 Administration of 3-methyladenine (3MA), an inhibitor of class III PI3K, abolished autophagy during reperfusion, while employment of rapamycin, an inhibitor of mTORC1 (normally inducing autophagy), surprisingly weakened the induction of autophagy during reperfusion. Sirolimus 133-142 CREB regulated transcription coactivator 1 Mus musculus 160-166 24112984-2 2013 Site-specific analysis of mTORC1 substrates now suggests that the sequence composition of a phosphorylation site determines whether it is sensitive to rapamycin and starvation. Sirolimus 151-160 CREB regulated transcription coactivator 1 Mus musculus 26-32 23792225-3 2013 The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 151-157 23792225-3 2013 The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Sirolimus 84-93 CREB regulated transcription coactivator 1 Mus musculus 277-283 26824026-10 2013 We found that both rapamycin, a specific mTORC1 blocker, and PP242 a mTOR antagonist induce the arrest of myeloma cells irrespective of bortezomib sensitivity. Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 41-47 23580240-0 2013 Concurrent inhibition of PI3K and mTORC1/mTORC2 overcomes resistance to rapamycin induced apoptosis by down-regulation of Mcl-1 in mantle cell lymphoma. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 34-40 23580240-6 2013 We demonstrate that inhibition of mTORC1 by rapamycin or blocking of mTORC1 and mTORC2 in conjunction with PI3K by NVP-BEZ235 reduces proliferation of MCL cell lines to a similar extent. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 34-40 23938603-8 2013 Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCalpha, in vascular tumor cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 26-32 23880314-6 2013 Inhibition of TORC1-dependent signal pathways by rapamycin from 8 wk suppressed the decline in mitochondria and exercise endurance observed when mice were fed the high-protein diet in association with preserved AMPK activity. Sirolimus 49-58 CREB regulated transcription coactivator 1 Mus musculus 14-19 23720219-11 2013 Rapamycin treatment after seizure onset reduced TORC1 activity and fully abolished the seizures. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 48-53 23924694-7 2013 Map4k4 silencing in cultured adipocytes elevates both the total protein expression and cleavage of sterol-regulated element binding protein-1 (Srebp-1) in a rapamycin-sensitive manner, consistent with Map4k4 signaling via mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 157-166 CREB regulated transcription coactivator 1 Mus musculus 265-271 23742760-5 2013 We show that inhibition of mTORC1 with rapamycin causes a reduction of PrP(Sc) accumulation at similar low levels as seen when the interaction between the translation initiation factors eIF4E and eIF4G downstream mTORC1 is inhibited using 4EGI-1. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 27-33 23742760-5 2013 We show that inhibition of mTORC1 with rapamycin causes a reduction of PrP(Sc) accumulation at similar low levels as seen when the interaction between the translation initiation factors eIF4E and eIF4G downstream mTORC1 is inhibited using 4EGI-1. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 213-219 23673367-3 2013 Both complexes are sensitive to a pharmacological inhibitor, torin1, although only mTORC1 is inhibited by rapamycin. Sirolimus 106-115 CREB regulated transcription coactivator 1 Mus musculus 83-89 23108404-5 2013 The endoplasmic reticulum Ca(2+) sensor, stromal interaction molecule 1 (STIM1), was upregulated in Tsc2-deficient cells, and was suppressed by mTORC1 inhibitor rapamycin. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 144-150 24277558-10 2013 Following extensive research on the pathologic activation of the mTORC1 pathway, an initial way of halting progression has been found in using mTORC1 inhibitors (Sirolimus, Everolimus). Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 65-71 24277558-10 2013 Following extensive research on the pathologic activation of the mTORC1 pathway, an initial way of halting progression has been found in using mTORC1 inhibitors (Sirolimus, Everolimus). Sirolimus 162-171 CREB regulated transcription coactivator 1 Mus musculus 143-149 23643747-4 2013 This effect was abolished by rapamycin, an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1), or by PF470867, a selective inhibitor of the p70 ribosomal S6 kinase 1 (S6K1). Sirolimus 29-38 CREB regulated transcription coactivator 1 Mus musculus 101-107 23820898-10 2013 Myometrial proliferation and mTORC1/S6 activity were abrogated by the mTORC1 inhibitor rapamycin or by elimination of sex steroid production through ovariectomy or aromatase inhibition. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 29-35 23820898-10 2013 Myometrial proliferation and mTORC1/S6 activity were abrogated by the mTORC1 inhibitor rapamycin or by elimination of sex steroid production through ovariectomy or aromatase inhibition. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 70-76 23832089-6 2013 Conversely, Notch gain of function causes fatty liver through constitutive activation of mTorc1, an effect that is reversible by treatment with rapamycin. Sirolimus 144-153 CREB regulated transcription coactivator 1 Mus musculus 89-95 23991179-1 2013 Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 47-53 23922392-7 2013 In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet beta-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Sirolimus 225-234 CREB regulated transcription coactivator 1 Mus musculus 51-57 23922392-7 2013 In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet beta-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Sirolimus 225-234 CREB regulated transcription coactivator 1 Mus musculus 252-258 23963659-10 2013 Suppression of mTORC1 activity was sufficient for sorafenib to hinder glucose utilization in breast cancer cells, as demonstrated by the observation that the mTORC1 inhibitor rapamycin induced a comparable down-regulation of GLUT-1 expression and glucose uptake. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 15-21 23963659-10 2013 Suppression of mTORC1 activity was sufficient for sorafenib to hinder glucose utilization in breast cancer cells, as demonstrated by the observation that the mTORC1 inhibitor rapamycin induced a comparable down-regulation of GLUT-1 expression and glucose uptake. Sirolimus 175-184 CREB regulated transcription coactivator 1 Mus musculus 158-164 23759595-5 2013 To further define the role of mTORC1 cascade in AKT/Ras induced HCC development, the mTORC1 inhibitor Rapamycin was administered to AKT/Ras mice at the time when small tumors started to emerge in the liver. Sirolimus 102-111 CREB regulated transcription coactivator 1 Mus musculus 85-91 23744068-5 2013 Refeeding after starvation with a standard mouse chow rapidly suppressed autophagy in both tissues, and this suppression was inhibited by rapamycin administration almost completely in the liver and partially in muscle, confirming that mTORC1 is indeed a crucial regulator in vivo. Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 235-241 23520131-9 2013 The inflammatory responses in SNRK knockdown adipocytes can be partially attributable to defective mTORC1 signaling, since rapamycin treatment activates IKKbeta and induces lipolysis in adipocytes. Sirolimus 123-132 CREB regulated transcription coactivator 1 Mus musculus 99-105 23376634-3 2013 This was indicated by treatment with the mTORC1 inhibitor rapamycin, which suppressed both S6 kinase and 4E-BP1 phosphorylation (dephosphorylated 4E-BP1 binds and inactivates eIF4E), or by knockdown of eIF4E. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 41-47 23585690-8 2013 Rapamycin-induced inhibition of mammalian/mechanistic target of rapamycin complex 1 (mTORC1), a mediator of the feeding/insulin signal to induce lipogenesis, reduced FAS phosphorylation, increased cytoplasmic FAS enzyme activity, and increased PPARalpha target gene expression. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 85-91 23696882-2 2013 We found that rapamycin, an inhibitor of mTORC1, attenuated Cd-induced apoptosis in renal tubular cells. Sirolimus 14-23 CREB regulated transcription coactivator 1 Mus musculus 41-47 23661807-7 2013 These Rheb transgenic mice exhibited increased activation of mTORC1 signaling in both kidney tubular and interstitial cells as well as progressive interstitial renal fibrosis; rapamycin inhibited these effects. Sirolimus 176-185 CREB regulated transcription coactivator 1 Mus musculus 61-67 23855221-3 2013 The MILES trial has successfully demonstrated that sirolimus, a mTORC1 inhibitor, can stabilize pulmonary function in LAM, but its effect disappears once sirolimus is discontinued. Sirolimus 51-60 CREB regulated transcription coactivator 1 Mus musculus 64-70 23855221-4 2013 Limited ability of sirolimus may be due to concomitant activation of autophagy in LAM cells when mTORC1 activity is suppressed by sirolimus. Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 97-103 23855221-4 2013 Limited ability of sirolimus may be due to concomitant activation of autophagy in LAM cells when mTORC1 activity is suppressed by sirolimus. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 97-103 23730416-3 2013 On the basis of immunoblot analyses, whereas rapamycin only partially inhibited mTOR complex 1 (mTORC1) activity and had no effect on mTOR complex 2 (mTORC2), PP242 inhibited the activity of both mTOR-containing complexes. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 96-102 23723238-7 2013 In cancer cells with inactivating mutations in GATOR1, mTORC1 is hyperactive and insensitive to amino acid starvation, and such cells are hypersensitive to rapamycin, an mTORC1 inhibitor. Sirolimus 156-165 CREB regulated transcription coactivator 1 Mus musculus 170-176 23696882-12 2013 In vivo, administration with rapamycin suppressed activation of mTORC1 and JNK, but not eIF2alpha, in the kidney of Cd-treated mice. Sirolimus 29-38 CREB regulated transcription coactivator 1 Mus musculus 64-70 23691153-3 2013 Recently, the mammalian target of rapamycin complex 1 (mTORC1) pathway has been implicated in mechanisms of epileptogenesis and the mTORC1 inhibitor, rapamycin, has been proposed to have antiepileptogenic effects in preventing some types of epilepsy. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 55-61 23691153-6 2013 Controlled cortical impact injury caused immediate hyperactivation of the mTORC1 pathway lasting at least one week, which was reversed by rapamycin treatment. Sirolimus 138-147 CREB regulated transcription coactivator 1 Mus musculus 74-80 23536185-5 2013 Inhibition of mammalian target of rapamycin complex 1 (mTORC1), for example with rapamycin, increases Akt phosphorylation while inhibiting mTORC1 signaling. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 55-61 23536185-5 2013 Inhibition of mammalian target of rapamycin complex 1 (mTORC1), for example with rapamycin, increases Akt phosphorylation while inhibiting mTORC1 signaling. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 139-145 23479136-6 2013 Protracted sunitinib exposure in 786-Suni cells yielded an increase in p27 expression and a decreased sensitivity to rapamycin analogs, although mTORC1 function could be inhibited with rapamycin analogs. Sirolimus 185-194 CREB regulated transcription coactivator 1 Mus musculus 145-151 23470622-2 2013 The mTOR pathway involves two independent complexes, mTORC1 and mTORC2, which phosphorylate S6 kinase (S6K) and serine/threonine kinase (Akt), respectively, and differ in their sensitivity to rapamycin. Sirolimus 192-201 CREB regulated transcription coactivator 1 Mus musculus 53-59 23479136-9 2013 CONCLUSIONS: Rapamycin analogs inhibited mTORC1 downstream targets and yielded anti-proliferative effects in HCC and RCC cells. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 41-47 23147251-5 2013 MATERIALS AND METHODS: We used PP242, a dual inhibitor of mTORC1/mTORC2 and the mTORC1 specific inhibitor rapamycin. Sirolimus 106-115 CREB regulated transcription coactivator 1 Mus musculus 80-86 23250913-9 2013 Further mTORC1 inhibition with rapamycin hastened weakness, atrophy and vacuolation in VCP-IBM mice. Sirolimus 31-40 CREB regulated transcription coactivator 1 Mus musculus 8-14 23616120-3 2013 We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). Sirolimus 153-162 CREB regulated transcription coactivator 1 Mus musculus 130-136 23452608-4 2013 mTORC1 is sensitive to rapamycin (also known as sirolimus), a drug prescribed in case of organ transplantation (kidney) due to its immunosuppressive and anti-proliferative properties. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 0-6 23297825-2 2013 The mammalian target of rapamycin complex 1 (mTORC1) is rapamycin-sensitive and mediates temporal control of cell growth by regulating several cellular processes, such as translation, transcription, and nutrient transport while the mammalian target of rapamycin complex 2 (mTORC2) is in sensitive to rapamycin and is involved in spatial control of cell growth via cytoskeleton regulation. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 45-51 23452608-4 2013 mTORC1 is sensitive to rapamycin (also known as sirolimus), a drug prescribed in case of organ transplantation (kidney) due to its immunosuppressive and anti-proliferative properties. Sirolimus 48-57 CREB regulated transcription coactivator 1 Mus musculus 0-6 23273915-7 2013 Both a phosphorylation-defective 4E-BP1 mutant and the mTORC1 inhibitor rapamycin partially blocked the oncogenic effects of S6K1 short isoforms, suggesting that these are mediated by mTORC1 and 4E-BP1. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 55-61 23273915-7 2013 Both a phosphorylation-defective 4E-BP1 mutant and the mTORC1 inhibitor rapamycin partially blocked the oncogenic effects of S6K1 short isoforms, suggesting that these are mediated by mTORC1 and 4E-BP1. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 184-190 23184942-3 2013 mTORC1, which is directly inhibited by rapamycin, promotes cell growth by stimulating protein synthesis and inhibiting autophagy. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 0-6 23278901-6 2013 Finally, in a pharmacological challenge in vivo using the specific mTORC1 inhibitor, rapamycin, hair cycle initiation was delayed, suggesting a functional relevance of mTORC1 in anagen entry. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 67-73 23278901-6 2013 Finally, in a pharmacological challenge in vivo using the specific mTORC1 inhibitor, rapamycin, hair cycle initiation was delayed, suggesting a functional relevance of mTORC1 in anagen entry. Sirolimus 85-94 CREB regulated transcription coactivator 1 Mus musculus 168-174 23565163-3 2013 The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 132-138 24093774-3 2013 However, the dual nature of mTOR, existing in two multiprotein complexes mTORC1 and mTORC2 driven by different feedback loops, decreases the therapeutic effects of rapamycin, the specific mTOR inhibitor. Sirolimus 164-173 CREB regulated transcription coactivator 1 Mus musculus 73-79 22959478-1 2013 UNLABELLED: Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 34-40 23555865-4 2013 The mTOR inhibitor, Rapamycin, stabilizes lung function in LAM and decreases the volume of renal angiomyolipomas, but lung function declines and angiomyolipomas regrow when treatment is discontinued, suggesting that factors induced by mTORC1 inhibition may promote the survival of TSC2-deficient cells. Sirolimus 20-29 CREB regulated transcription coactivator 1 Mus musculus 235-241 23326514-6 2013 To study the functional and pathological roles of elevated mTORC1 signaling in the oocytes, we treated the Pten-mutant mice with the specific mTORC1 inhibitor rapamycin. Sirolimus 159-168 CREB regulated transcription coactivator 1 Mus musculus 59-65 23335988-9 2013 In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1(cko) ovaries. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 35-41 23335988-9 2013 In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1(cko) ovaries. Sirolimus 13-22 CREB regulated transcription coactivator 1 Mus musculus 107-113 23326514-6 2013 To study the functional and pathological roles of elevated mTORC1 signaling in the oocytes, we treated the Pten-mutant mice with the specific mTORC1 inhibitor rapamycin. Sirolimus 159-168 CREB regulated transcription coactivator 1 Mus musculus 142-148 22307455-5 2012 We further hypothesized that combining p-XSC with rapamycin, an mTORC1 inhibitor, would be an effective combinatory strategy for the inhibition of prostate cancer. Sirolimus 50-59 CREB regulated transcription coactivator 1 Mus musculus 64-70 23053656-8 2012 Subsequent studies revealed that NDGA may also direct target mTORC1 complex because NDGA suppressed amino acids- and insulin-stimulated mTORC1 and acted like rapamycin to disrupt mTOR-Raptor interaction. Sirolimus 158-167 CREB regulated transcription coactivator 1 Mus musculus 61-67 23089982-5 2012 Interestingly, despite apparent inactivation of the PI3K/AKT signaling pathway, resistant cells exhibited constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) and were highly sensitive to mTOR inhibition with rapamycin and the dual PI3K/mTOR inhibitor NVP-BEZ235. Sirolimus 153-162 CREB regulated transcription coactivator 1 Mus musculus 174-180 22700793-5 2012 Thus we employed a cell culture model of murine skeletal muscle and subjected the myotubes to CCA for 3 h per day for 4 consecutive days in the presence or absence of the mTORC1 inhibitor rapamycin. Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 171-177 22827930-5 2012 LH/hCG-mediated stimulation of the steroidogenic enzyme mRNA was blocked by the mTORC1 inhibitor, rapamycin. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 80-86 22827930-7 2012 Furthermore, pharmacological targeting of mTORC1 with rapamycin also blocked LH/hCG- or forskolin-induced expression of cAMP response element-binding protein (CREB) and steroidogenic enzymes (P450 side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and 17alpha-hydroxylase/17,20 lyase) but produced no effect on steroidogenic acute regulatory protein levels. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 42-48 22973301-0 2012 Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 105-111 22973301-1 2012 Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 43-49 22973301-7 2012 Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 24-30 22973301-7 2012 Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 180-186 22700793-7 2012 Rapamycin-mediated inhibition of mTORC1 did not suppress these CCA-induced increases in mitochondrial proteins and organelle content. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 33-39 22496407-4 2012 The activity of mTOR complex 1 (mTORC1) is necessary for renal regeneration and repair after AKI, and inhibition of mTORC1 by rapamycin has been shown to delay recovery from ischemic AKI in animal studies, and to prolong delayed graft function in humans who have received a kidney transplant. Sirolimus 126-135 CREB regulated transcription coactivator 1 Mus musculus 116-122 22696593-4 2012 In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 42-48 22696593-4 2012 In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance. Sirolimus 185-194 CREB regulated transcription coactivator 1 Mus musculus 42-48 22820188-6 2012 To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. Sirolimus 134-143 CREB regulated transcription coactivator 1 Mus musculus 113-119 24358826-1 2012 The recent development of mammalian target of rapamycin (mTOR) kinase domain inhibitors and genetic dissection of rapamycin-sensitive and -insensitive mTOR protein complexes (mTORC1 and mTORC2) have revealed that phosphorylation of the mTOR substrate 4E-BP1 on amino acids Thr37 and/or Thr46 represents a rapamycin-insensitive activity of mTORC1. Sirolimus 46-55 CREB regulated transcription coactivator 1 Mus musculus 339-345 22843885-6 2012 Phosphorylation of mTORC1 substrate, p70S6K at thr389 was reduced by rapamycin and pretreatment with rapamycin abrogated platelet-derived growth factor (PDGF)-induced activation of S6K, as well as that of mTORC2 substrate pAKT(Ser473). Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 19-25 22843885-6 2012 Phosphorylation of mTORC1 substrate, p70S6K at thr389 was reduced by rapamycin and pretreatment with rapamycin abrogated platelet-derived growth factor (PDGF)-induced activation of S6K, as well as that of mTORC2 substrate pAKT(Ser473). Sirolimus 101-110 CREB regulated transcription coactivator 1 Mus musculus 19-25 22837538-5 2012 Pharmacologic reversal of elevated mTORC1 signaling by rapamycin improves cardiac and skeletal muscle function and enhances survival in mice lacking A-type lamins. Sirolimus 75-84 CREB regulated transcription coactivator 1 Mus musculus 55-61 22837538-7 2012 In addition, inhibition of mTORC1 signaling with rapamycin improves defective autophagic-mediated degradation in Lmna(-/-) mice. Sirolimus 69-78 CREB regulated transcription coactivator 1 Mus musculus 47-53 22532572-3 2012 Hamartin and tuberin form a heterodimer that inhibits the mammalian target of rapamycin complex 1 (mTORC1) kinase, a major cellular regulator of protein translation, cell growth and proliferation. Sirolimus 78-87 CREB regulated transcription coactivator 1 Mus musculus 99-105 22532572-4 2012 Hyperactivated mTORC1 signaling, an important feature of TSC, has prompted a number of preclinical and clinical studies with the mTORC1 inhibitor rapamycin. Sirolimus 146-155 CREB regulated transcription coactivator 1 Mus musculus 15-21 22532572-4 2012 Hyperactivated mTORC1 signaling, an important feature of TSC, has prompted a number of preclinical and clinical studies with the mTORC1 inhibitor rapamycin. Sirolimus 146-155 CREB regulated transcription coactivator 1 Mus musculus 129-135 22496482-7 2012 Rapamycin decreased the proliferation of ovarian cancer cells, and this was accompanied by inhibition of the phosphorylation of S6, a protein used as readout of mTORC1 function. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 161-167 21826653-7 2012 Conversely, the effect of T(3) on SREBP-1 level was enhanced by using rapamycin, mTOR-C1 inhibitor. Sirolimus 70-79 CREB regulated transcription coactivator 1 Mus musculus 81-88 22519596-11 2012 Rapamycin, an inhibitor of mTORC1, significantly reversed the suppressive effects of eIF2alpha on NF-kappaB. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 27-33 22452883-0 2012 Inhibition of mTORC1 kinase activates Smads 1 and 5 but not Smad8 in human prostate cancer cells, mediating cytostatic response to rapamycin. Sirolimus 131-140 CREB regulated transcription coactivator 1 Mus musculus 14-20 22452883-2 2012 Here, we show that rapamycin activates Smads 1 and 5 in human prostate cancer cells and tissues through blocking mTORC1 kinase. Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 113-119 22496482-8 2012 However, rapamycin had only a marginal effect on the phosphorylation status of 4E-BP1, another mTORC1 substrate. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 95-101 22496482-9 2012 Therefore, mTORC1 probably controls p4E-BP1 along two distinct pathways, one of them sensitive to rapamycin and another insensitive. Sirolimus 98-107 CREB regulated transcription coactivator 1 Mus musculus 11-17 22758368-1 2012 Treatment with rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1) can increase mammalian life span. Sirolimus 15-24 CREB regulated transcription coactivator 1 Mus musculus 83-89 22080835-5 2012 We found that mitophagy could be induced following treatment with the mTORC1 inhibitor rapamycin in cybrids carrying either large-scale partial deletions of mtDNA or complete depletion of mtDNA. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 70-76 22355179-4 2012 PI3K inhibition by LY294002 increased NIS-mediated radioiodide uptake (RAIU) mainly through upregulation of NIS expression, however, mTORC1 inhibition by Rapamycin did not increase NIS-mediated RAIU despite increased NIS protein levels. Sirolimus 154-163 CREB regulated transcription coactivator 1 Mus musculus 133-139 22457328-2 2012 By assembling with unique and shared partner proteins, mTOR forms the catalytic core of at least two complexes, mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to modulate cell growth, proliferation, survival, and metabolism in response to diverse environmental cues. Sirolimus 216-225 CREB regulated transcription coactivator 1 Mus musculus 128-134 22428559-4 2012 Rapamycin inhibits some mTORC1 functions, whereas mTOR-KIs (mTOR kinase inhibitors) interfere with all of them. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 24-30 22560223-5 2012 Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 187-192 22314813-7 2012 Although rapamycin acutely inhibited mTOR complex 1 (mTORC1), the toxic effects of rapamycin were more closely correlated to the dissociation and inactivation of mTORC2 and the inhibition of PKB. Sirolimus 9-18 CREB regulated transcription coactivator 1 Mus musculus 53-59 22466652-5 2012 Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Sirolimus 87-96 CREB regulated transcription coactivator 1 Mus musculus 108-114 22461615-2 2012 Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 113-119 22347189-9 2012 The importance of understanding the role of this signaling pathway in the development of addiction vulnerability is underscored by the fact that the mTORC1 inhibitor rapamycin reduces drug-seeking in pre-clinical models and preliminary evidence indicating that rapamycin suppresses drug craving in humans. Sirolimus 166-175 CREB regulated transcription coactivator 1 Mus musculus 149-155 22121221-3 2012 We used a new non-radioactive labeling approach to study the effects of rapamycin, an inhibitor of mTORC1, on rRNA synthesis. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 99-105 22070140-5 2012 Treatment with the specific mTORC1 [mTOR (mammalian target of rapamycin) complex 1] inhibitor rapamycin or siRNA (small interfering RNA) knockdown of mTOR destabilized the ODC mRNA, but rapamycin had only a minor effect on ODC translation initiation. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 28-34 22675606-7 2012 The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Sirolimus 116-125 CREB regulated transcription coactivator 1 Mus musculus 167-173 22227194-6 2012 These defects are phenocopied by inhibiting mTORC1 activity with rapamycin. Sirolimus 65-74 CREB regulated transcription coactivator 1 Mus musculus 44-50 21779001-2 2012 We found that rapamycin, an inhibitor of mTOR complex 1 (mTORC1), attenuated endoplasmic reticulum (ER) stress-induced apoptosis. Sirolimus 14-23 CREB regulated transcription coactivator 1 Mus musculus 57-63 22863860-3 2012 The effects of OA on mTORC1 activation, cell proliferation, and cell-cycle progression to S and G2/M phases were completely reversed by rapamycin. Sirolimus 136-145 CREB regulated transcription coactivator 1 Mus musculus 21-27 22080480-2 2012 Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-lived. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 56-62 22102284-9 2012 Moreover, adult hippocampal NP proliferation induced by HU-308 and excitotoxicity was blocked by the mTORC1 inhibitor rapamycin. Sirolimus 118-127 CREB regulated transcription coactivator 1 Mus musculus 101-107 22408430-2 2012 mTORC1 is sensitive to rapamycin, activates S6K1 and 4EBP1, which are involved in mRNA translation. Sirolimus 23-32 CREB regulated transcription coactivator 1 Mus musculus 0-6 23185517-2 2012 mTORC1 inhibitors have shown limited efficacy in the clinic, largely attributed to the reactivation of Akt due to rapamycin induced mTORC2 activity. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 0-6 22916036-4 2012 Treatment with rapamycin, an inhibitor of mTORC1 activity, decreased tumor burden in adult Lkb1 mutant mice. Sirolimus 15-24 CREB regulated transcription coactivator 1 Mus musculus 42-48 23272222-6 2012 Rapamycin, a mTORC1 inhibitor, restores the insulin signaling after downregulation of REDD1 expression. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 13-19 23272152-9 2012 mTORC1 activity was sensitive to LY294002 and rapamycin or transfection of cells with GRP78 dsRNA. Sirolimus 46-55 CREB regulated transcription coactivator 1 Mus musculus 0-6 23209838-5 2012 Pretreatment with PI3K inhibitor (Ly294002), Akt inhibitor, or mTORC1 inhibitor (rapamycin) blocked the HGF-induced VEGF-A production. Sirolimus 81-90 CREB regulated transcription coactivator 1 Mus musculus 63-69 22768106-9 2012 Indeed mTORC1 inhibitor rapamycin prevented HSF1-S326 phosphorylation, suggesting that this complex is involved in HSF1 regulation in stress. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 7-13 22880048-4 2012 Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167) or mTORC1 inhibitor (rapamycin) induced AKT phosphorylation (pAKT) and downstream signal activation. Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 91-97 22071574-10 2011 This study reveals that the apoptotic effect of rapamycin requires doses that completely dissociate Raptor from mTORC1 and suppress that phosphorylation of 4E-BP1 and inhibit eIF4E. Sirolimus 48-57 CREB regulated transcription coactivator 1 Mus musculus 112-118 22363765-6 2012 Results were compared to vehicle treatment and treatment with the mTORC1 inhibitor rapamycin for 1 month. Sirolimus 83-92 CREB regulated transcription coactivator 1 Mus musculus 66-72 23461035-4 2012 Induction of senescence closely correlates with the activation of the complex mTORC1, as it was shown by inhibiting mTORC1 with rapamycin. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 78-84 23461035-4 2012 Induction of senescence closely correlates with the activation of the complex mTORC1, as it was shown by inhibiting mTORC1 with rapamycin. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 116-122 21911485-1 2011 A variety of mechanisms confer hypersensitivity of tumor cells to the macrolide rapamycin, the prototypic mTORC1 inhibitor. Sirolimus 80-89 CREB regulated transcription coactivator 1 Mus musculus 106-112 21785113-3 2011 mTORC1 activity is sensitive to the selective inhibitor rapamycin, whereas mTORC2 is resistant. Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 0-6 22025690-2 2011 Using mutant mice, mimicking aspects of human preterm birth, we show here that uterine decidual senescence early in pregnancy via heightened mammalian target of rapamycin complex 1 (mTORC1) signaling is a significant contributor of preterm birth and fetal death, and that these adverse phenotypes are rescued by a low dose of rapamycin, an inhibitor of mTORC1 signaling. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 182-188 21854390-8 2011 In our neuronal cell model, allosteric inhibition of mTORC1 by everolimus, a rapamycin analogue, did not induce autophagy or affect aggregate degradation. Sirolimus 77-86 CREB regulated transcription coactivator 1 Mus musculus 53-59 21973019-2 2011 Recent studies in such models revealed that inhibiting mTORC1 with rapamycin effectively suppressed seizure activity. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 55-61 22028687-9 2011 Finally, administration of rapamycin, a drug which blocks mTORC1, results in a strong reduction of LID. Sirolimus 27-36 CREB regulated transcription coactivator 1 Mus musculus 58-64 21806543-3 2011 Rapamycin selectively targets mTORC1 function, and the emergence of specific ATP-competitive kinase inhibitors has enabled assessment of dual mTORC1 and mTORC2 blockade. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 30-36 21862237-0 2011 mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan diets. Sirolimus 120-129 CREB regulated transcription coactivator 1 Mus musculus 0-6 21806970-3 2011 We have now shown that medium rich in branched-chain amino acids stimulates expression of the SREBP1c gene in cultured hepatocytes in a manner sensitive both to rapamycin, a pharmacological inhibitor of mTORC1, and to a short hairpin RNA (shRNA) specific for S6 kinase 1 (S6K1), a downstream effector of mTORC1. Sirolimus 161-170 CREB regulated transcription coactivator 1 Mus musculus 304-310 21733825-3 2011 Rapamycin, an established mTORC1 inhibitor, was used to further explore the role of mTORC1 signaling in epithelial carcinogenesis, specifically during the tumor promotion stage. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 26-32 21851176-4 2011 The Food and Drug Administration (FDA)-approved immunosuppressive macrolide rapamycin binds immunophilin FKBP12 (FK506-binding protein) to inhibit mTORC1. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 147-153 21851176-5 2011 Unlike most other interventions tested to date, inhibition of mTORC1 by rapamycin extends life span in old mice, likely by a combination of increased autophagy and decreased mRNA translation. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 62-68 21592956-4 2011 Both PP242 and Torin1 blocked thrombin and insulin-like growth factor 1-mediated Akt Ser(473) phosphorylation with an IC(50) between 1 and 5 nm, whereas the mTORC1 inhibitor rapamycin had no effect. Sirolimus 174-183 CREB regulated transcription coactivator 1 Mus musculus 157-163 21508335-4 2011 Here, we demonstrate that the inhibition of mTORC1 by rapamycin (mTORC1 inhibitor), torin1 (both mTORC1 and mTORC2 inhibitor) or short hairpin RNA-mediated knockdown of mTOR, regulatory associated protein of mTOR (RAPTOR), and p70 S6 kinase (p70S6K) increased basal NT release via upregulating NT gene expression in BON cells. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 44-50 21415215-8 2011 Inhibition of the mTOR catalytic site with OSI-027 results in suppression of both mTORC2 and RI-mTORC1 complexes and elicits much more potent antileukemic responses than selective mTORC1 targeting with rapamycin. Sirolimus 202-211 CREB regulated transcription coactivator 1 Mus musculus 180-186 21561413-2 2011 mTOR complex 1 (mTORC1) is potently inhibited by the immunosupressive macrolide rapamycin; whereas, mTORC2 is insensitive to this durg. Sirolimus 80-89 CREB regulated transcription coactivator 1 Mus musculus 16-22 21733825-9 2011 Overall, the data indicate that rapamycin is a potent inhibitor of skin tumor promotion and suggest that signaling through mTORC1 contributes significantly to the process of skin tumor promotion. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 123-129 21076853-0 2011 mTORC1 activation in childhood ependymoma and response to sirolimus. Sirolimus 58-67 CREB regulated transcription coactivator 1 Mus musculus 0-6 21525172-3 2011 This study investigated the efficacy and safety of the mTORC1 inhibitor sirolimus for treatment of renal angiomyolipomas in patients with these disorders. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 55-61 21338617-6 2011 Inhibition of phosphatidylinositol 3-kinase or Akt with LY 294002 or Akti-1/2 stimulates HSP27 phosphorylation while rapamycin, which inhibits mTORC1, does not. Sirolimus 117-126 CREB regulated transcription coactivator 1 Mus musculus 143-149 21576371-3 2011 Rapamycin, an allosteric mTORC1 inhibitor, does not antagonize equally these outputs, but the reason for this is unknown. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 25-31 21576371-5 2011 Rapamycin exposure destabilizes mTORC1, but in cell lines where autophagy is drug insensitive, higher levels of mTOR-bound raptor are detected than in cells where rapamycin stimulates autophagy. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 32-38 21576371-7 2011 Importantly, nonefficacious concentrations of an ATP-competitive mTOR inhibitor can be combined with rapamycin to synergistically inhibit mTORC1 and activate autophagy but leave mTORC2 signaling intact. Sirolimus 101-110 CREB regulated transcription coactivator 1 Mus musculus 138-144 21419848-3 2011 These proteins form a heterodimer that inhibits the mammalian target of rapamycin complex 1 (mTORC1) pathway, controlling translation and cell growth. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 93-99 21419848-10 2011 The cell death and ER stress phenotypes were rescued by treatment with the mTORC1 inhibitor rapamycin. Sirolimus 92-101 CREB regulated transcription coactivator 1 Mus musculus 75-81 21525000-4 2011 Short rapamycin treatment specifically inhibiting mTORC1 suppressed p70 but not p85 phosphorylation, suggesting that p85 might be directly activated by phosphatidic acid. Sirolimus 6-15 CREB regulated transcription coactivator 1 Mus musculus 50-56 21651786-8 2011 We also show that IGF-1 increases the expression of leptin and reverses the Abeta42-induced attenuation in leptin expression via the activation of mTORC1 signaling as the mTORC1 inhibitor rapamycin completely precluded the IGF-1-induced increase in leptin expression. Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 147-153 21651786-8 2011 We also show that IGF-1 increases the expression of leptin and reverses the Abeta42-induced attenuation in leptin expression via the activation of mTORC1 signaling as the mTORC1 inhibitor rapamycin completely precluded the IGF-1-induced increase in leptin expression. Sirolimus 188-197 CREB regulated transcription coactivator 1 Mus musculus 171-177 21557327-4 2011 mTOR exists in two distinct complexes-mTORC1 and mTORC2 that differ in their components and sensitivity to rapamycin. Sirolimus 107-116 CREB regulated transcription coactivator 1 Mus musculus 38-44 21368105-5 2011 Suppression of mTORC2 signaling with siRNA rictor, or inhibition of mTORC1 signaling with rapamycin and metformin, while having little effect on other complex activities, inhibited VSM-H and chronic hypoxia-induced human and rat PAVSM cell proliferation. Sirolimus 90-99 CREB regulated transcription coactivator 1 Mus musculus 68-74 20821325-1 2011 Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an anticancer agent. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 33-39 21321189-7 2011 These effects were abolished by mTORC1 inhibition by rapamycin in human HepG2 cells. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 32-38 21430254-4 2011 The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. Sirolimus 129-138 CREB regulated transcription coactivator 1 Mus musculus 111-117 21430254-6 2011 In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 147-153 21331075-3 2011 However, allosteric inhibition of mTORC1 by rapamycin has only modest effects in T-cell acute lymphoblastic leukemia (T-ALL). Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 34-40 21240477-7 2011 Remarkably, rapamycin resistance was found to affect specifically the mTORC1/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) branch of the mTORC1 pathway in the presence of 50 mumol/l oleate. Sirolimus 12-21 CREB regulated transcription coactivator 1 Mus musculus 70-76 21240477-7 2011 Remarkably, rapamycin resistance was found to affect specifically the mTORC1/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) branch of the mTORC1 pathway in the presence of 50 mumol/l oleate. Sirolimus 12-21 CREB regulated transcription coactivator 1 Mus musculus 150-156 21258412-5 2011 A careful examination of preclinical and clinical studies performed with rapamycin or derivatives thereof shows that although results are encouraging, we are only half way in the long and winding road to design rationale treatment targeted at the LKB1/AMPK/TSC/mTORC1 pathway. Sirolimus 73-82 CREB regulated transcription coactivator 1 Mus musculus 261-267 21266843-6 2011 The allosteric mTORC1 inhibitor rapamycin fails to induce apoptosis in conjunction with blockade of autophagy, due to feedback-activation of Akt. Sirolimus 32-41 CREB regulated transcription coactivator 1 Mus musculus 15-21 21428917-2 2011 Rapamycin inhibits some of the functions of mTORC1, whereas newly developed mTOR kinase inhibitors interfere with the actions of both types of complex. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 44-50 20943770-5 2011 Phosphorylated S6 (p-S6) ribosomal protein, a marker of mTORC1 activity, was increased in Cy/+ rats compared with normal littermate controls (+/+) and decreased by rapamycin. Sirolimus 164-173 CREB regulated transcription coactivator 1 Mus musculus 56-62 21048785-3 2011 Here, we studied the effect of targeting the PI3K/mTORC1/mTORC2 pathway by PI-103 and rapamycin in melanoma cells and in a melanoma mouse model. Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 50-56 21048785-5 2011 Combined treatment with PI-103 and the prototypic mTORC1 inhibitor rapamycin led to the synergistic suppression of AKT and ribosomal S6 protein phosphorylation and to the induction of apoptosis. Sirolimus 67-76 CREB regulated transcription coactivator 1 Mus musculus 50-56 21203451-8 2010 We then assessed selected compounds that stimulate autophagy and found that the antihelmintic chemical niclosamide prevents large aggregate formation induced by proteasome inhibition, while the prototypical mTORC1 inhibitor rapamycin had no apparent effect. Sirolimus 224-233 CREB regulated transcription coactivator 1 Mus musculus 207-213 21651476-4 2011 Rapamycin, the selective and allosteric inhibitor of mTOR, inhibits the enzyme in mTORC1, but not in mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 82-88 21949767-11 2011 RESULTS: Whereas the treatment with rapamycin persistently inhibited mTORC1 signaling, it suppressed only partially the cell growth. Sirolimus 36-45 CREB regulated transcription coactivator 1 Mus musculus 69-75 21949767-12 2011 MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion of MNK markedly suppressed proliferation of the CTCL cells when combined with the rapamycin-mediated inhibition of mTORC1. Sirolimus 156-165 CREB regulated transcription coactivator 1 Mus musculus 189-195 21200439-3 2010 METHODOLOGY/PRINCIPAL FINDINGS: Mice were treated with the mTORC1 inhibitor rapamycin or vehicle prior to lethal endotoxin challenge. Sirolimus 76-85 CREB regulated transcription coactivator 1 Mus musculus 59-65 21200439-7 2010 We found that mTORC1-S6K suppression by rapamycin delayed mortality of mice challenged with lethal endotoxin, and was associated with dampened circulating levels of VEGF, IL-1beta, IFN-gamma and IL-5. Sirolimus 40-49 CREB regulated transcription coactivator 1 Mus musculus 14-20 20980505-5 2011 Instead, HCMV-induced PABP accumulation resulted from new protein synthesis and was sensitive to the mTORC1-selective inhibitor rapamycin, which interferes with phosphorylation of the mTORC1 substrate p70 S6K and the translational repressor 4E-BP1. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 101-107 20980505-5 2011 Instead, HCMV-induced PABP accumulation resulted from new protein synthesis and was sensitive to the mTORC1-selective inhibitor rapamycin, which interferes with phosphorylation of the mTORC1 substrate p70 S6K and the translational repressor 4E-BP1. Sirolimus 128-137 CREB regulated transcription coactivator 1 Mus musculus 184-190 20813961-5 2010 In this study, we show that tuberin regulates the localization of E-cadherin via an Akt/mTORC1/CLIP170-dependent, rapamycin-sensitive pathway. Sirolimus 114-123 CREB regulated transcription coactivator 1 Mus musculus 88-94 20937815-10 2010 The results suggest that rapamycin inhibits cell motility at least in part by down-regulation of RhoA protein expression and activity through mTORC1-mediated S6K1 and 4E-BP1-signaling pathways. Sirolimus 25-34 CREB regulated transcription coactivator 1 Mus musculus 142-148 21042876-0 2010 mTORC1 inhibition via rapamycin promotes triacylglycerol lipolysis and release of free fatty acids in 3T3-L1 adipocytes. Sirolimus 22-31 CREB regulated transcription coactivator 1 Mus musculus 0-6 21042876-2 2010 Numerous clinical trials employing the mTORC1 inhibitor rapamycin (aka sirolimus) to immuno-suppress patients following organ transplantation have documented the development of hypertriglyceridemia and elevated serum free fatty acids (FFA). Sirolimus 56-65 CREB regulated transcription coactivator 1 Mus musculus 39-45 21042876-2 2010 Numerous clinical trials employing the mTORC1 inhibitor rapamycin (aka sirolimus) to immuno-suppress patients following organ transplantation have documented the development of hypertriglyceridemia and elevated serum free fatty acids (FFA). Sirolimus 71-80 CREB regulated transcription coactivator 1 Mus musculus 39-45 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 96-102 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 158-167 CREB regulated transcription coactivator 1 Mus musculus 96-102 21075311-5 2010 On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1-dependent, but PI3K and AKT-independent manner, resulting in resistance. Sirolimus 37-46 CREB regulated transcription coactivator 1 Mus musculus 20-26 20798356-8 2010 Changes in pancreatic weight and RNA content were completely inhibited, and changes in protein content were partially abated, when the mTORC1 inhibitor rapamycin was administered during high-protein chow feeding. Sirolimus 152-161 CREB regulated transcription coactivator 1 Mus musculus 135-141 20464435-5 2010 In time course experiments with the mTORC1 inhibitor rapamycin we here demonstrate rapamycin-resistant phosphorylation of the ribosomal protein S6 at S240/244. Sirolimus 53-62 CREB regulated transcription coactivator 1 Mus musculus 36-42 20976781-2 2010 Rats were treated or not with rapamycin, an mTORC1 inhibitor. Sirolimus 30-39 CREB regulated transcription coactivator 1 Mus musculus 44-50 20554235-5 2010 Co-administration of the mTORC1 inhibitor rapamycin with rhGAA in a GAA knockout mouse reduced muscle glycogen content more than rhGAA or rapamycin alone. Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 25-31 20686448-9 2010 Hence, our study found that inhibition of mTORC1 by sirolimus correlated with decreased renal cyst growth in this model of human ADPKD but had no effect on the decline in renal function. Sirolimus 52-61 CREB regulated transcription coactivator 1 Mus musculus 42-48 20631133-9 2010 The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Sirolimus 190-199 CREB regulated transcription coactivator 1 Mus musculus 83-89 20935470-8 2010 Rapamycin, a specific inhibitor of mTORC1 kinase, decreased cellular hypertrophy, canceled coffilin phosphorylation and partially restored cell migration in p21(Waf1+/+) cells. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 35-41 20670375-10 2010 On the other hand, Rapamycin, an allosteric inhibitor of mTORC1, down-regulates leptin expression, increases tau phosphorylation, and does not affect Akt and GSK-3beta. Sirolimus 19-28 CREB regulated transcription coactivator 1 Mus musculus 57-63 20660299-8 2010 Pharmacologic targeting of mTORC1 with rapamycin also abrogated hCG or FSK-induced phosphorylation of S6K1, rpS6, and eukaryotic initiation factor 4E binding protein 1. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 27-33 20581466-3 2010 Recent evidence indicates that L-DOPA-induced dyskinesia (LID) is associated with persistent activation of the mammalian target of rapamycin complex 1 (mTORC1) in the medium spiny neurons (MSNs) of the striatum, the main component of the basal ganglia. Sirolimus 131-140 CREB regulated transcription coactivator 1 Mus musculus 152-158 20600147-8 2010 Sirolimus inhibited the mTORC1 pathway, while the PPAR-gamma agonist rosiglitazone enhanced PP2Ac and reduced p70S6K. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 24-30 20600147-10 2010 Sirolimus and rosiglitazone in combination down-regulated the mTORC1 pathway and over-activated PP2Ac in diabetic kidney. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 62-68 20616057-2 2010 Despite extensive work on the functional relevance of rapamycin-sensitive mTORC1 complexes, much less is known on the roles of rapamycin-insensitive (RI) complexes, including mTORC2 and RI-mTORC1, in BCR-ABL-leukemogenesis. Sirolimus 54-63 CREB regulated transcription coactivator 1 Mus musculus 74-80 20581466-6 2010 Using a mouse model of LID, we recently showed that administration of the allosteric mTORC1 inhibitor, rapamycin, reduces dyskinesia. Sirolimus 103-112 CREB regulated transcription coactivator 1 Mus musculus 85-91 20597028-4 2010 The efficacy of derivatives of the natural product rapamycin (sirolimus), which functions as an allosteric inhibitor of mTORC1, has validated mTOR inhibition as an anticancer treatment. Sirolimus 62-71 CREB regulated transcription coactivator 1 Mus musculus 120-126 20299475-7 2010 These changes were observed despite normal activation of the insulin receptor substrate/PI 3-kinase/Akt axis in liver of rapamycin-treated rats, as expected from the blockade of the mTORC1/S6K1 negative feedback loop. Sirolimus 121-130 CREB regulated transcription coactivator 1 Mus musculus 182-188 20457610-2 2010 mTORC1, which is directly inhibited by rapamycin, promotes cell growth by stimulating protein synthesis and inhibiting autophagy. Sirolimus 39-48 CREB regulated transcription coactivator 1 Mus musculus 0-6 20138985-9 2010 Inhibition of mTORC1 by rapamycin or amino acid deprivation partially abrogated insulin-mediated PRAS40-Ser183 phosphorylation in cultured cell lines. Sirolimus 24-33 CREB regulated transcription coactivator 1 Mus musculus 14-20 20496258-2 2010 The discovery of the involvement of rapamycin-insensitive mTOR complex 2 (mTORC2) in the activation of Akt, combined with the limited clinical antitumor activity of mTOR complex 1 (mTORC1)-directed rapamycin analogs, have led to the discovery of ATP-competitive selective inhibitors of the mTOR kinase that inhibit the function of both mTORC1 and mTORC2. Sirolimus 198-207 CREB regulated transcription coactivator 1 Mus musculus 181-187 20299475-2 2010 Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive. Sirolimus 91-100 CREB regulated transcription coactivator 1 Mus musculus 73-79 20512842-2 2010 In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Sirolimus 72-81 CREB regulated transcription coactivator 1 Mus musculus 51-57 20512842-0 2010 Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 56-62 20512842-4 2010 We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. Sirolimus 33-42 CREB regulated transcription coactivator 1 Mus musculus 91-97 20512842-7 2010 Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells. Sirolimus 86-95 CREB regulated transcription coactivator 1 Mus musculus 76-82 19951971-7 2010 Moreover, mTORC1 inhibition using sirolimus overactivates PI3K/AKT via the upregulation of IRS2 expression and by favoring IGF-1/IGF-1R autocrine signaling. Sirolimus 34-43 CREB regulated transcription coactivator 1 Mus musculus 10-16 20371605-4 2010 Glycolysis in FoxO3a-deficient cells was associated with increased S6K1 phosphorylation and was sensitive to rapamycin, an inhibitor of the mTORC1 pathway that has been linked to glycolysis regulation. Sirolimus 109-118 CREB regulated transcription coactivator 1 Mus musculus 140-146 20116405-1 2010 Inhibition of mTORC1 with the mTOR inhibitor rapamycin may lead to an induction of Akt phosphorylation in cancer cells via mTORC2 activation. Sirolimus 45-54 CREB regulated transcription coactivator 1 Mus musculus 14-20 20181700-2 2010 However, the phosphorylation of mTORC1 targets is differentially sensitive to the mTORC1 inhibitor rapamycin, and the drug inhibits HCMV replication to a modest extent. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 32-38 20181700-2 2010 However, the phosphorylation of mTORC1 targets is differentially sensitive to the mTORC1 inhibitor rapamycin, and the drug inhibits HCMV replication to a modest extent. Sirolimus 99-108 CREB regulated transcription coactivator 1 Mus musculus 82-88 19443154-1 2010 PURPOSE: New evidence is emerging that the availability of nutrients plays a key role in regulating the mammalian target of rapamycin complex-1 (mTORC1) signaling pathway in human cancers. Sirolimus 124-133 CREB regulated transcription coactivator 1 Mus musculus 145-151 20022946-8 2010 Although insulin stimulates both mTORC1- and mTORC2-associated mTOR Ser(P)-2481 in a phosphatidylinositol 3-kinase-dependent manner, rapamycin acutely inhibits insulin-stimulated mTOR Ser(P)-2481 in mTORC1 but not mTORC2. Sirolimus 133-142 CREB regulated transcription coactivator 1 Mus musculus 199-205 20203102-3 2010 Acute inhibition of mTORC1/S6K1 by rapamycin increases insulin signaling and glucose uptake in myocytes and adipocytes, but whether these effects can be maintained under chronic inhibition of mTORC1 or S6K1 remains unclear. Sirolimus 35-44 CREB regulated transcription coactivator 1 Mus musculus 20-26 20022946-10 2010 These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity. Sirolimus 173-182 CREB regulated transcription coactivator 1 Mus musculus 24-30 20022946-10 2010 These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity. Sirolimus 173-182 CREB regulated transcription coactivator 1 Mus musculus 192-198 20022946-10 2010 These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity. Sirolimus 173-182 CREB regulated transcription coactivator 1 Mus musculus 192-198 20160076-6 2010 Importantly, elevated ROS and dysregulation of mTORC1 in ATM-deficient cells is inhibited by rapamycin, which also rescues lymphomagenesis in Atm-deficient mice. Sirolimus 93-102 CREB regulated transcription coactivator 1 Mus musculus 47-53 20005306-3 2010 Rapamycin and its analogs (rapalogs) function as allosteric inhibitors of mTORC1 and are currently used in the treatment of advanced renal cell carcinoma. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 74-80 20013896-7 2010 We previously reported that aberrant mTORC1 activation leads to supernumerary centrosomes, a phenotype rescued by the mTORC1 inhibitor rapamycin. Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 37-43 20013896-7 2010 We previously reported that aberrant mTORC1 activation leads to supernumerary centrosomes, a phenotype rescued by the mTORC1 inhibitor rapamycin. Sirolimus 135-144 CREB regulated transcription coactivator 1 Mus musculus 118-124 20133650-6 2010 In contrast, subnanomolar concentrations of rapamycin, an inhibitor of the mTORC1 kinase, blocked insulin induction of SREBP-1c, but had no effect on insulin suppression of PEPCK. Sirolimus 44-53 CREB regulated transcription coactivator 1 Mus musculus 75-81 20048174-0 2010 Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. Sirolimus 42-51 CREB regulated transcription coactivator 1 Mus musculus 142-148 21326806-4 2010 mTORC1 is sensitive to the selective inhibitor rapamycin. Sirolimus 47-56 CREB regulated transcription coactivator 1 Mus musculus 0-6 20068177-2 2010 Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Sirolimus 0-9 CREB regulated transcription coactivator 1 Mus musculus 108-114 19864431-5 2010 We report that insulin promotes mTORC1-associated phosphorylation of raptor Ser(863) via the canonical PI3K/TSC/Rheb pathway in a rapamycin-sensitive manner. Sirolimus 130-139 CREB regulated transcription coactivator 1 Mus musculus 32-38