PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33189285-2 2021 The mammalian target of rapamycin/eukaryotic initiation factor 4E (mTOR/eIF4E) signaling pathway is involved in fat synthesis. Sirolimus 24-33 eukaryotic translation initiation factor 4E Homo sapiens 72-77 34255842-3 2021 First, we use capCLIP to identify the eIF4E cap-omes in human cells with/without the mTORC1 (mechanistic target of rapamycin, complex 1) inhibitor rapamycin, there being an emerging consensus that rapamycin inhibits translation of TOP (terminal oligopyrimidine) mRNAs by displacing eIF4E from their caps. Sirolimus 197-206 eukaryotic translation initiation factor 4E Homo sapiens 282-287 35349401-11 2022 Also, it is demonstrated that Vpg interacts with eIF4E and that rapamycin treatment partially diminishes the viral protein synthesis. Sirolimus 64-73 eukaryotic translation initiation factor 4E Homo sapiens 49-54 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 eukaryotic translation initiation factor 4E Homo sapiens 145-188 25659819-4 2015 Rapamycin inhibits the phosphorylation of S6K at nano-molar concentrations in MDA-MB-231 cells; however, micro-molar concentrations of rapamycin are required to inhibit phosphorylation of 4E-BP1 - the phosphorylation of which liberates eIF4E to initiate translation. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 236-241 25659819-4 2015 Rapamycin inhibits the phosphorylation of S6K at nano-molar concentrations in MDA-MB-231 cells; however, micro-molar concentrations of rapamycin are required to inhibit phosphorylation of 4E-BP1 - the phosphorylation of which liberates eIF4E to initiate translation. Sirolimus 135-144 eukaryotic translation initiation factor 4E Homo sapiens 236-241 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 eukaryotic translation initiation factor 4E Homo sapiens 25-30 31782083-4 2020 While we show that phosphorylation pattern of eIF4E responds faithfully to Rapamycin inhibition, the prolonged exposure to Rapamycin rescues the loss of eIF4E phosphorylation through Mnk1 activation. Sirolimus 75-84 eukaryotic translation initiation factor 4E Homo sapiens 46-51 31782083-4 2020 While we show that phosphorylation pattern of eIF4E responds faithfully to Rapamycin inhibition, the prolonged exposure to Rapamycin rescues the loss of eIF4E phosphorylation through Mnk1 activation. Sirolimus 123-132 eukaryotic translation initiation factor 4E Homo sapiens 153-158 31782083-5 2020 We also present evidence that eIF4E interacts with the amino terminal domain of S6K1 in a phospho-dependent manner, and this interaction is instrumental in overriding Rapamycin inhibition of S6K1. Sirolimus 167-176 eukaryotic translation initiation factor 4E Homo sapiens 30-35 31921404-0 2020 TSC patient-derived isogenic neural progenitor cells reveal altered early neurodevelopmental phenotypes and rapamycin-induced MNK-eIF4E signaling. Sirolimus 108-117 eukaryotic translation initiation factor 4E Homo sapiens 130-135 31921404-10 2020 Rapamycin also increased MNK1/2-eIF4E signaling in TSC1-deficient NPCs. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 32-37 30552925-0 2019 Eukaryotic Initiation Factor 4E (eIF4E) sequestration mediates 4E-BP1 response to rapamycin. Sirolimus 82-91 eukaryotic translation initiation factor 4E Homo sapiens 0-31 30552925-0 2019 Eukaryotic Initiation Factor 4E (eIF4E) sequestration mediates 4E-BP1 response to rapamycin. Sirolimus 82-91 eukaryotic translation initiation factor 4E Homo sapiens 33-38 30552925-6 2019 The data presented in this study identifies eIF4E and not Raptor as a cellular factor responsible to regulate rapamycin sensitivity of 4E-BP1 suggesting that the phosphorylation dynamics and rapamycin sensitivity of 4E-BP1 and S6K1 are regulated independently. Sirolimus 110-119 eukaryotic translation initiation factor 4E Homo sapiens 44-49 30297804-4 2018 We showed that rapamycin and its analog RAD001 (everolimus) exerted only mild inhibition on the viability of Jurkat, CEM and Molt-4 cell lines (for everolimus the maximum inhibition was <40% at 100 nM), but greatly enhanced the phosphorylation of eIF4E, a downstream substrate of MAPK-interacting kinase (MNK) that was involved in promoting cell survival. Sirolimus 15-24 eukaryotic translation initiation factor 4E Homo sapiens 250-255 29850566-12 2018 Rapamycin elicited concentration-dependent reductions in the mRNA (P < 0.05) and protein (P < 0.01) expressions of Smad2 and eIF-4E. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 131-137 27245614-5 2016 Furthermore, rapamycin disrupted eIF4E function selectively in lymphocytes, which was due to the increased abundance of 4E-BP2 relative to that of 4E-BP1 in these cells and the greater sensitivity of 4E-BP2 to rapamycin. Sirolimus 13-22 eukaryotic translation initiation factor 4E Homo sapiens 33-38 27050281-3 2016 Rapamycin induces eIF4E phosphorylation by activating MAPK-interacting kinases (Mnks), and therefore targeting Mnk/eIF4E pathway represents a potential therapeutic strategy for the treatment of NSCLC. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 18-23 27050281-3 2016 Rapamycin induces eIF4E phosphorylation by activating MAPK-interacting kinases (Mnks), and therefore targeting Mnk/eIF4E pathway represents a potential therapeutic strategy for the treatment of NSCLC. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 115-120 25439783-7 2015 TE2 cells are sensitized to rapamycin treatment after overexpression of 4E-BP1 or knockdown of eIF4E; TE1 cells become resistant to rapamycin after knockdown of 4E-BP1 or overexpression of eIF4E. Sirolimus 28-37 eukaryotic translation initiation factor 4E Homo sapiens 95-100 25439783-7 2015 TE2 cells are sensitized to rapamycin treatment after overexpression of 4E-BP1 or knockdown of eIF4E; TE1 cells become resistant to rapamycin after knockdown of 4E-BP1 or overexpression of eIF4E. Sirolimus 28-37 eukaryotic translation initiation factor 4E Homo sapiens 189-194 25439783-8 2015 These data suggest that the 4E-BP1/eIF4E ratio is a determinant for the response of TE1 and TE2 cells to rapamycin treatment. Sirolimus 105-114 eukaryotic translation initiation factor 4E Homo sapiens 35-40 25439783-12 2015 Thus, the 4E-BP1/eIF4E ratio may represent a therapeutic index for the prediction of clinical outcome of rapamycin treatment in patients with esophageal squamous cell carcinoma. Sirolimus 105-114 eukaryotic translation initiation factor 4E Homo sapiens 17-22 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 eukaryotic translation initiation factor 4E Homo sapiens 227-232 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 eukaryotic translation initiation factor 4E Homo sapiens 190-195 21576371-6 2011 Using small interfering RNA (siRNA), we find that knockdown of raptor relieves autophagy and the eIF4E effector pathway from rapamycin resistance. Sirolimus 125-134 eukaryotic translation initiation factor 4E Homo sapiens 97-102 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 eukaryotic translation initiation factor 4E Homo sapiens 175-180 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 eukaryotic translation initiation factor 4E Homo sapiens 202-207 23376634-9 2013 These data indicate that the cytostatic effect of rapamycin is suppression of both S6 kinase and eIF4E, while the cytotoxic effects are due suppression of eIF4E in the absence of S6 kinase-dependent activation of TGF-beta signals. Sirolimus 50-59 eukaryotic translation initiation factor 4E Homo sapiens 97-102 22767218-8 2012 Moreover, direct targeting of eIF4F with constitutively active 4E-BP1 is significantly more potent in collaboration with bortezomib than rapamycin. Sirolimus 137-146 eukaryotic translation initiation factor 4E Homo sapiens 30-35 22071574-5 2011 We report here that the apoptotic effects of high-dose rapamycin treatment correlate with suppressing phosphorylation of the mTOR complex 1 substrate, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4E-BP1). Sirolimus 55-64 eukaryotic translation initiation factor 4E Homo sapiens 151-182 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 eukaryotic translation initiation factor 4E Homo sapiens 175-180 23831578-0 2013 Rapamycin enhances eIF4E phosphorylation by activating MAP kinase-interacting kinase 2a (Mnk2a). Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 19-24 23831578-3 2013 Rapamycin increases eIF4E phosphorylation in cancer cells, potentially limiting their anti-cancer effects. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 20-25 23831578-4 2013 Here we show that the rapamycin-induced increase in eIF4E phosphorylation reflects increased activity of Mnk2 but not Mnk1. Sirolimus 22-31 eukaryotic translation initiation factor 4E Homo sapiens 52-57 23872707-4 2013 We report here that hippuristanol (Hipp), a translation initiation inhibitor that selectively inhibits the eIF4F RNA helicase subunit, eIF4A, resensitizes Emu-Myc lymphomas to DNA damaging agents, including those that overexpress eIF4E-a modifier of rapamycin responsiveness. Sirolimus 250-259 eukaryotic translation initiation factor 4E Homo sapiens 107-112 22556409-11 2012 Since pp242 was more potent than rapamycin in causing sequestering of eIF-4E, a TORC1/4E-BP1/eIF-4E-mediated mechanism of ERK activation could explain the greater effectiveness of pp242. Sirolimus 33-42 eukaryotic translation initiation factor 4E Homo sapiens 70-76 20177775-5 2010 Rapamycin and its analogues are known to inhibit mTOR pathway; however, they also show simultaneous upregulation of Akt and eIF4E survival pathways on inhibition of mTOR, rendering cells more resistant to rapamycin treatment. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 124-129 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 eukaryotic translation initiation factor 4E Homo sapiens 24-29 20664001-7 2010 It is noteworthy that the mammalian target of rapamycin (mTOR) inhibitor rapamycin also induced phosphorylation of eIF4E in a Mnk-dependent manner, whereas inhibition strongly enhanced its antileukemic effects. Sirolimus 46-55 eukaryotic translation initiation factor 4E Homo sapiens 115-120 20177775-7 2010 Our results show that combination treatment of rapamycin with isoflavones, especially biochanin A at 50 muM, decreased the phosphorylation of Akt and eIF4E proteins and rendered U87 cells more sensitive to rapamycin treatment when compared to cells treated with rapamycin alone. Sirolimus 47-56 eukaryotic translation initiation factor 4E Homo sapiens 150-155 20177775-5 2010 Rapamycin and its analogues are known to inhibit mTOR pathway; however, they also show simultaneous upregulation of Akt and eIF4E survival pathways on inhibition of mTOR, rendering cells more resistant to rapamycin treatment. Sirolimus 205-214 eukaryotic translation initiation factor 4E Homo sapiens 124-129 20177775-6 2010 In this study we investigated the effect of combination treatment of rapamycin with isoflavones such as genistein and biochanin A on mTOR pathway and activation of Akt and eIF4E in human glioblastoma (U87) cells. Sirolimus 69-78 eukaryotic translation initiation factor 4E Homo sapiens 172-177 18981735-9 2008 Moreover, the presence of erlotinib suppressed rapamycin-induced phosphorylation of Akt, ERK and eIF4E as well, implying that erlotinib can suppress mTOR inhibition-induced feedback activation of several survival signaling pathways including Akt, ERK and eIF4E. Sirolimus 47-56 eukaryotic translation initiation factor 4E Homo sapiens 255-260 18809972-4 2008 In contrast, eIF4E phosphorylation is low in PC3 and LNCaP cells with mutated PTEN and constitutively active AKT/mTOR pathway, but it can be strongly induced through inhibition of mTOR activity by rapamycin or serum depletion. Sirolimus 197-206 eukaryotic translation initiation factor 4E Homo sapiens 13-18 19641186-4 2009 Subsequent investigations revealed that rapamycin also activated eIF4E and the mTORC2 target Akt, suggesting a potential mechanism of rapamycin resistance. Sirolimus 40-49 eukaryotic translation initiation factor 4E Homo sapiens 65-70 18981735-9 2008 Moreover, the presence of erlotinib suppressed rapamycin-induced phosphorylation of Akt, ERK and eIF4E as well, implying that erlotinib can suppress mTOR inhibition-induced feedback activation of several survival signaling pathways including Akt, ERK and eIF4E. Sirolimus 47-56 eukaryotic translation initiation factor 4E Homo sapiens 97-102 18082048-1 2007 OBJECTIVE: This study examined the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to identify the drug target for treatment of viral myocarditis. Sirolimus 45-54 eukaryotic translation initiation factor 4E Homo sapiens 143-150 18361417-5 2008 Rapamycin was found to prevent dissociation of 4E-BP from the initiation factor eIF4E and to suppress correlatively a burst of global protein synthesis occurring at the G2/M transition. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 80-85 18701474-6 2008 Expression of wild-type eIF4E in rapamycin-treated E6/E7/hTert/HRas(V12) and U373 cells failed to rescue colony formation, although expression of wild-type S6K1 or rapamycin-resistant S6K1 in rapamycin-treated U373 and U251 provided partial rescue. Sirolimus 33-42 eukaryotic translation initiation factor 4E Homo sapiens 24-29 18644990-3 2008 Rapamycin inhibits translation initiation by decreasing the phosphorylation of 4E-BP1, increasing eIF4E/4E-BP1 interaction. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 98-103 18644990-8 2008 eIF4E knockdown inhibited the growth of cells with varying total and phosphorylated 4E-BP1 levels and inhibited rapamycin-insensitive as well as rapamycin-sensitive cell lines. Sirolimus 112-121 eukaryotic translation initiation factor 4E Homo sapiens 0-5 18644990-8 2008 eIF4E knockdown inhibited the growth of cells with varying total and phosphorylated 4E-BP1 levels and inhibited rapamycin-insensitive as well as rapamycin-sensitive cell lines. Sirolimus 145-154 eukaryotic translation initiation factor 4E Homo sapiens 0-5 16103051-8 2005 Paradoxically, rapamycin also concurrently increased the phosphorylation of both Akt and eIF4E. Sirolimus 15-24 eukaryotic translation initiation factor 4E Homo sapiens 89-94 17382186-8 2007 Although eIF4E overexpression has been suggested to make cells resistant to rapamycin, we observed marked growth inhibition with rapamycin as a single agent in SKRC39, which has marked overexpression of eIF4E. Sirolimus 76-85 eukaryotic translation initiation factor 4E Homo sapiens 9-14 17382186-8 2007 Although eIF4E overexpression has been suggested to make cells resistant to rapamycin, we observed marked growth inhibition with rapamycin as a single agent in SKRC39, which has marked overexpression of eIF4E. Sirolimus 129-138 eukaryotic translation initiation factor 4E Homo sapiens 203-208 16715128-13 2006 Rapamycin inhibits IGF-I-stimulated cell motility, through suppression of both S6K1 and 4E-BP1/eIF4E-signaling pathways, as a consequence of inhibition of mTOR kinase activity. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 95-100 16242075-7 2005 Individually, EKI-785 diminishes while rapamycin promotes the binding of the translation inhibitor eukaryotic initiation factor 4E binding protein (4EBP1) to the eukaryotic translation initiation factor 4E (eIF4E). Sirolimus 39-48 eukaryotic translation initiation factor 4E Homo sapiens 162-205 16242075-7 2005 Individually, EKI-785 diminishes while rapamycin promotes the binding of the translation inhibitor eukaryotic initiation factor 4E binding protein (4EBP1) to the eukaryotic translation initiation factor 4E (eIF4E). Sirolimus 39-48 eukaryotic translation initiation factor 4E Homo sapiens 207-212 16103051-9 2005 The rapamycin-induced phosphorylation of Akt and eIF4E was suppressed by the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002, suggesting the requirement of PI3K in this process. Sirolimus 4-13 eukaryotic translation initiation factor 4E Homo sapiens 49-54 15355912-10 2004 Rapamycin analogs can potentially be used as adjuvant therapy for patients with eIF4E-positive margins. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 80-85 15292274-5 2004 Surprisingly, although rapamycin, RAD001, wortmannin, and LY294002 inhibited the phosphorylation of 4E-BP1 and its release from eIF4E, they did not prevent the recovery of translation rates. Sirolimus 23-32 eukaryotic translation initiation factor 4E Homo sapiens 128-133 15190216-3 2004 Interestingly, lymphomas expressing Akt, but not those expressing Bcl-2 are sensitized to chemotherapy-induced apoptosis by the mTOR inhibitor rapamycin, an effect that is countered by eIF4E. Sirolimus 143-152 eukaryotic translation initiation factor 4E Homo sapiens 185-190 10212283-7 1999 PGF2alpha-induced phosphorylation of eIF4E and 4E-BP1 was also found to be sensitive to inhibition by both wortmannin and rapamycin. Sirolimus 122-131 eukaryotic translation initiation factor 4E Homo sapiens 37-53 11847216-0 2002 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. Sirolimus 142-151 eukaryotic translation initiation factor 4E Homo sapiens 40-71 10454551-6 1999 Moreover, despite rapamycin-induced dephosphorylation of 4BP-1, eIF-4E-eIF-4G complexes (eIF-4F) were still detected. Sirolimus 18-27 eukaryotic translation initiation factor 4E Homo sapiens 64-70 10454551-6 1999 Moreover, despite rapamycin-induced dephosphorylation of 4BP-1, eIF-4E-eIF-4G complexes (eIF-4F) were still detected. Sirolimus 18-27 eukaryotic translation initiation factor 4E Homo sapiens 89-95 9458731-6 1998 Both rapamycin and wortmannin completely blocked the insulin-induced changes in 4E-BP1 phosphorylation and association of 4E-BP1 and eIF-4E; PD-98059 had no effect on either parameter. Sirolimus 5-14 eukaryotic translation initiation factor 4E Homo sapiens 133-139 9160663-6 1997 Growth factor-induced phosphorylation of 4E-BP1 and dissociation of 4E-BP1 from eIF-4E was blocked in cells treated with rapamycin, wortmannin, or PD098059. Sirolimus 121-130 eukaryotic translation initiation factor 4E Homo sapiens 80-86 8599949-7 1996 Thus, inactivation of eIF-4E is, at least in part, responsible for inhibition of cap-dependent translation in rapamycin-treated cells. Sirolimus 110-119 eukaryotic translation initiation factor 4E Homo sapiens 22-28 7629182-7 1995 Moreover, rapamycin attenuated the stimulation of PHAS-I phosphorylation by insulin and markedly inhibited dissociation of PHAS-I.eIF-4E, without decreasing MAP kinase activity. Sirolimus 10-19 eukaryotic translation initiation factor 4E Homo sapiens 130-136 7629182-11 1995 Rapamycin may inhibit translation initiation by increasing PHAS-I binding to eIF-4E. Sirolimus 0-9 eukaryotic translation initiation factor 4E Homo sapiens 77-83