PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 18539384-3 2008 In addition, LMP1 abolished the potentials of retinoic acid (RA) to down-regulate Cdk2 and Cdk4 and to up-regulate p16, p21, and p27, resulting in activation of E2F1 in the presence of RA. Tretinoin 46-59 cyclin dependent kinase 2 Homo sapiens 82-86 18539384-3 2008 In addition, LMP1 abolished the potentials of retinoic acid (RA) to down-regulate Cdk2 and Cdk4 and to up-regulate p16, p21, and p27, resulting in activation of E2F1 in the presence of RA. Tretinoin 61-63 cyclin dependent kinase 2 Homo sapiens 82-86 16766008-6 2006 In addition, CAPE enhanced ATRA-induced cell cycle arrest at the G1 phase by decreasing the association of cdk2-cyclin E complex. Tretinoin 27-31 cyclin dependent kinase 2 Homo sapiens 107-111 18773862-6 2008 Consistent with the inhibition effect and G1 arrest, ATRA and SB, alone or in combination, induced the expression of G1 phase markers cyclin-dependent kinase (CDK) 6, p21, and p27; inhibited the expression of S-G2 phase proteins CDK2; and decreased Rb phosphorylation. Tretinoin 53-57 cyclin dependent kinase 2 Homo sapiens 229-233 18773862-9 2008 These results indicate that the growth inhibition and G1 arrest of oral squamous carcinoma cells in response to ATRA and/or SB correlates with the induction of G1 phase cell cycle regulatory proteins CDK6, p21, and p27 and the inhibition of S-G2 phase cell cycle regulatory protein CDK2. Tretinoin 112-116 cyclin dependent kinase 2 Homo sapiens 282-286 17960384-0 2008 Combination of all-trans retinoic acid and interferon-gamma upregulated p27(kip1) and down regulated CDK2 to cause cell cycle arrest leading to differentiation and apoptosis in human glioblastoma LN18 (PTEN-proficient) and U87MG (PTEN-deficient) cells. Tretinoin 25-38 cyclin dependent kinase 2 Homo sapiens 101-105 18006504-2 2008 In this study, RA is found to cause MAPK activation with sustained association of RAF to MEK or ERK, leading to a MAPK-dependent accumulation of p21(Waf1/Cip1) and binding to CDK2 blocking G(1)/S transition. Tretinoin 15-17 cyclin dependent kinase 2 Homo sapiens 175-179 15715961-0 2005 CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma cells. Tretinoin 16-29 cyclin dependent kinase 2 Homo sapiens 0-4 16765349-7 2006 Data presented here suggest a novel RA-signaling, by which RA-induced p21 induction and complex formation with cyclin E/CDK2 diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis. Tretinoin 36-38 cyclin dependent kinase 2 Homo sapiens 120-124 16765349-7 2006 Data presented here suggest a novel RA-signaling, by which RA-induced p21 induction and complex formation with cyclin E/CDK2 diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis. Tretinoin 36-38 cyclin dependent kinase 2 Homo sapiens 133-137 15715961-4 2005 Our findings suggested that the growth inhibition of RA in HCC cells differed according to G(1) phase delay by CDK2 or 4, finally induction of apoptosis. Tretinoin 53-55 cyclin dependent kinase 2 Homo sapiens 111-115 15715961-6 2005 RA treatment caused cell cycle arrest at G(1) and decreased the expressions and activities of CDK2 or CDK4 in RA-sensitive HepG2 and SNU354 cells. Tretinoin 0-2 cyclin dependent kinase 2 Homo sapiens 94-98 15715961-7 2005 On the other hand, RA-resistant Hep3B and SNU449 cells progressed into the S/G(2)+M phase and showed increased CDK2 and CDK4 expression and activity. Tretinoin 19-21 cyclin dependent kinase 2 Homo sapiens 111-115 15715961-8 2005 Since the inhibition of CDK2 or 4 activities resulted in sensitization of HCC cells to RA, the combination of RA and compounds of inhibiting CDKs such as UCN01 and flavopiridol might be a useful targeted therapy strategy for HCC. Tretinoin 87-89 cyclin dependent kinase 2 Homo sapiens 24-28 14587026-1 2003 All-trans retinoic acid (ATRA) can down regulate the anti-apoptotic protein Bcl-2 and the cell cycle proteins cyclin D1 and cdk2 in estrogen receptor-positive breast cancer cells. Tretinoin 0-23 cyclin dependent kinase 2 Homo sapiens 124-128 15587392-9 2004 ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 70-74 14587026-1 2003 All-trans retinoic acid (ATRA) can down regulate the anti-apoptotic protein Bcl-2 and the cell cycle proteins cyclin D1 and cdk2 in estrogen receptor-positive breast cancer cells. Tretinoin 25-29 cyclin dependent kinase 2 Homo sapiens 124-128 10896783-6 2000 Evaluation of the kinase activity of cyclin-Cdk complexes showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Tretinoin 70-72 cyclin dependent kinase 2 Homo sapiens 155-159 12421932-5 2002 The presence of atRA led to elevated levels of cyclin D3, -E, and -A, decreased levels of p27(Kip1), increased activity of cyclin-dependent kinase 2, and enhanced phosphorylation of the retinoblastoma protein (pRB). Tretinoin 16-20 cyclin dependent kinase 2 Homo sapiens 123-148 11753676-6 2001 Also, RA treatment increased expression of the cdk inhibitor p27 and decreased activity of cdk 2, cdk 4 and cdk 6. Tretinoin 6-8 cyclin dependent kinase 2 Homo sapiens 91-96 11063125-3 2000 We report that RA enhances p27 expression, which results in increased association with cyclin E/cyclin-dependent kinase 2 complexes and suppression of their activity; however, antisense clones, which have greatly reduced RA-dependent p27 inducibility (NT2-p27AS), continue to synthesize DNA and are unable to differentiate properly in response to RA as determined by lack of neurite outgrowth and by the failure to modify surface antigens. Tretinoin 15-17 cyclin dependent kinase 2 Homo sapiens 96-121 12012012-7 2002 Our results indicate that ATRA-pretreatment modified the CDDP-induced regulation of CDK2 activity by the CDK inhibitors p21 and p27. Tretinoin 26-30 cyclin dependent kinase 2 Homo sapiens 84-88 12012012-7 2002 Our results indicate that ATRA-pretreatment modified the CDDP-induced regulation of CDK2 activity by the CDK inhibitors p21 and p27. Tretinoin 26-30 cyclin dependent kinase 2 Homo sapiens 84-87 12012012-8 2002 Taken together, our findings suggest that ATRA potentiates the apoptosis induced by CDDP in ovarian carcinoma cells and that this action is sustained by modulation of the activity of CDK2/cyclin A. Tretinoin 42-46 cyclin dependent kinase 2 Homo sapiens 183-187 11753686-6 2001 These studies demonstrated that both atRA and BMS453 induce Rb hypophosphorylation and decrease CDK2 kinase activity. Tretinoin 37-41 cyclin dependent kinase 2 Homo sapiens 96-100 11030153-7 2000 These results suggest that complex regulation of CDKs play a key role in G1 arrest of ML-1 after treatment with ATRA and GM-CSF. Tretinoin 112-116 cyclin dependent kinase 2 Homo sapiens 49-53 11030153-8 2000 We also showed that an increase in CDK2-bound p27 and CDK4-bound p18 are caused by treatment with ATRA and a decrease in CDK6-bound cyclin D3 is induced synergistically by treatment with both reagents. Tretinoin 98-102 cyclin dependent kinase 2 Homo sapiens 35-39 10896783-6 2000 Evaluation of the kinase activity of cyclin-Cdk complexes showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Tretinoin 70-72 cyclin dependent kinase 2 Homo sapiens 206-210 10094816-6 1999 Olomoucine, a potent p34(cdc2) and Cdk2 inhibitor, effectively blocked RA-mediated p34(cdc2) kinase activation and prevented RA-induced apoptosis. Tretinoin 71-73 cyclin dependent kinase 2 Homo sapiens 35-39 10644979-4 2000 Our findings demonstrate that the retinoic acid-dependent growth arrest of LAN-5 neuroblastoma cell line is associated to a very large accumulation (>tenfold) of p27Kip1 protein, a cyclin-dependent kinase inhibitor; the protein binds and inhibits cyclin-dependent kinase 2, 4 and 6 activities, thus hampering pRb and p107 phosphorylation. Tretinoin 34-47 cyclin dependent kinase 2 Homo sapiens 250-275 10706449-8 1999 The levels of CDK2 activity were inhibited approximately 60% in ATRA-treated cells, suggesting that the increased p21 levels were sufficient to inhibit CDK activity and cause RB hypophosphorylation. Tretinoin 64-68 cyclin dependent kinase 2 Homo sapiens 14-17 10438723-8 1999 Thus, retinoic acid induced a rapid, but transient increased binding of p21(Cip1) to CDK2. Tretinoin 6-19 cyclin dependent kinase 2 Homo sapiens 85-89 10706449-6 1999 ATRA decreased the level of phosphorylation of the RB protein at doses > 5 x 10(-9) M and also induced a five fold increase in p21WAF1, while levels of p27KIP1 and CDK2 were unchanged. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 167-171 10706449-8 1999 The levels of CDK2 activity were inhibited approximately 60% in ATRA-treated cells, suggesting that the increased p21 levels were sufficient to inhibit CDK activity and cause RB hypophosphorylation. Tretinoin 64-68 cyclin dependent kinase 2 Homo sapiens 14-18 9716179-10 1998 RXR-gamma expression produced significant reduction in levels of RA-responsive genes including the cyclin-dependent kinase inhibitors p21Cip1/WAF1 and p27Kip1, resulting in increased cdc2 and cdk2 kinase activity and RB phosphorylation. Tretinoin 65-67 cyclin dependent kinase 2 Homo sapiens 192-196 10094816-4 1999 In addition, RA had no effect on the levels of Bcl-XL; Bcl-XS; cyclins A, B, D1, D3, or E; or Rb1 expression but markedly down-modulated Cdk2 kinase activity and reduced Cdk4 expression. Tretinoin 13-15 cyclin dependent kinase 2 Homo sapiens 137-141 9778049-3 1998 Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. Tretinoin 20-22 cyclin dependent kinase 2 Homo sapiens 146-150 9778049-3 1998 Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. Tretinoin 20-22 cyclin dependent kinase 2 Homo sapiens 152-156 9778049-5 1998 In addition, RA-treated LCLs showed a marked up-regulation of the CDK inhibitor (CKI) p27Kip-1 at the protein but not mRNA level, which correlated with a progressive increase of p27Kip-1 in CDK2 complexes (more than 2.5-fold) and with a reduction in the active phosphorylated form of CDK2. Tretinoin 13-15 cyclin dependent kinase 2 Homo sapiens 190-194 9778049-5 1998 In addition, RA-treated LCLs showed a marked up-regulation of the CDK inhibitor (CKI) p27Kip-1 at the protein but not mRNA level, which correlated with a progressive increase of p27Kip-1 in CDK2 complexes (more than 2.5-fold) and with a reduction in the active phosphorylated form of CDK2. Tretinoin 13-15 cyclin dependent kinase 2 Homo sapiens 284-288 9778049-9 1998 Overall, these results demonstrate that RA treatment of EBV-immortalized B lymphocytes is associated with multiple effects on G1 regulatory proteins, including p27Kip1 up-regulation, decreased levels of cyclins D2, D3 and A, and inhibition of CDK2, CDK4 and CDK6 activity, which ultimately result in reduced pRb phosphorylation and G0/G1 growth arrest. Tretinoin 40-42 cyclin dependent kinase 2 Homo sapiens 243-247 11601206-0 1999 [Study of the role of cyclin-dependent kinases (CDKs) in retinoic acid (RA) inducing HL-60 cell differentiation]. Tretinoin 57-70 cyclin dependent kinase 2 Homo sapiens 48-52 11601206-0 1999 [Study of the role of cyclin-dependent kinases (CDKs) in retinoic acid (RA) inducing HL-60 cell differentiation]. Tretinoin 72-74 cyclin dependent kinase 2 Homo sapiens 48-52 11601206-3 1999 Meanwhile, histone H1 kinase assay was used to observe the changes of CDK2 activities in HL-60 cells treatment with ATRA and AE. Tretinoin 116-120 cyclin dependent kinase 2 Homo sapiens 70-74 11601206-6 1999 The activities of cyclin E/CDK2 and the amounts of cyclin D1/CDK4 complexes were decreased in ATRA- or AE-treated HL-60 cells. Tretinoin 94-98 cyclin dependent kinase 2 Homo sapiens 27-31 11601206-7 1999 CONCLUSION: The effects of RA on the proliferation and differentiation of HL-60 cells may be associated with significant decreases in the activities of CDKs. Tretinoin 27-29 cyclin dependent kinase 2 Homo sapiens 152-156 31740384-5 2020 We have determined that both the CDK2 depletion and pharmacological inhibitor of CDK2 significantly sensitize three subtypes of AML cells (including two non-APL cells) to ATRA-induced cell differentiation. Tretinoin 171-175 cyclin dependent kinase 2 Homo sapiens 33-37 9366521-3 1997 RA-induced cell cycle arrest is also associated with induction of p27Kip1 expression, inhibition of cdk2-associated kinase activity and alteration of the phosphorylation state of the pRB-family proteins. Tretinoin 0-2 cyclin dependent kinase 2 Homo sapiens 100-104 9259311-0 1997 CDK2 is a target for retinoic acid-mediated growth inhibition in MCF-7 human breast cancer cells. Tretinoin 21-34 cyclin dependent kinase 2 Homo sapiens 0-4 9259311-6 1997 While cdk4 activity was similar in control and RA-treated cells, cdk2 activity began to decrease within 48 h of exposure to RA and was profoundly reduced after 72 h. This reduced activity was associated with decreased phosphorylation of cdk2. Tretinoin 47-49 cyclin dependent kinase 2 Homo sapiens 65-69 9259311-6 1997 While cdk4 activity was similar in control and RA-treated cells, cdk2 activity began to decrease within 48 h of exposure to RA and was profoundly reduced after 72 h. This reduced activity was associated with decreased phosphorylation of cdk2. Tretinoin 47-49 cyclin dependent kinase 2 Homo sapiens 237-241 9259311-6 1997 While cdk4 activity was similar in control and RA-treated cells, cdk2 activity began to decrease within 48 h of exposure to RA and was profoundly reduced after 72 h. This reduced activity was associated with decreased phosphorylation of cdk2. Tretinoin 124-126 cyclin dependent kinase 2 Homo sapiens 65-69 9259311-8 1997 However, assays of cdk2 from pooled lysates from RA-treated and control cells showed that RA-treated cells contain a cdk2-inhibitory activity. Tretinoin 49-51 cyclin dependent kinase 2 Homo sapiens 19-23 17180006-6 1994 In this study we isolated RA-resistant 15N cell lines and analyzed their growth properties and changes in cell cycle related (cdc2, cdk2, cyclins A, B, D and E) and early response (fos and jun) gene expression to evaluate the role IGF2 may play in mediating RA resistance. Tretinoin 26-28 cyclin dependent kinase 2 Homo sapiens 132-136 9259311-8 1997 However, assays of cdk2 from pooled lysates from RA-treated and control cells showed that RA-treated cells contain a cdk2-inhibitory activity. Tretinoin 90-92 cyclin dependent kinase 2 Homo sapiens 19-23 9259311-8 1997 However, assays of cdk2 from pooled lysates from RA-treated and control cells showed that RA-treated cells contain a cdk2-inhibitory activity. Tretinoin 90-92 cyclin dependent kinase 2 Homo sapiens 117-121 9259311-9 1997 Our results show that RA inhibits cell cycle progression of MCF-7 cells by inhibiting cdk2 mRNA and protein production and by decreasing cdk2 activity. Tretinoin 22-24 cyclin dependent kinase 2 Homo sapiens 86-90 9259311-9 1997 Our results show that RA inhibits cell cycle progression of MCF-7 cells by inhibiting cdk2 mRNA and protein production and by decreasing cdk2 activity. Tretinoin 22-24 cyclin dependent kinase 2 Homo sapiens 137-141 8788034-6 1996 RA-induced reduction in Cdk2 activity was modest and occurred after %S phase declined, while Cdk4 activity was reduced, coincident with cell cycle changes. Tretinoin 0-2 cyclin dependent kinase 2 Homo sapiens 24-28 32032659-0 2020 Roscovitine enhances All-trans retinoic acid (ATRA)-induced leukemia cell differentiation: Novel effects on signaling molecules for a putative Cdk2 inhibitor. Tretinoin 46-50 cyclin dependent kinase 2 Homo sapiens 143-147 31740384-5 2020 We have determined that both the CDK2 depletion and pharmacological inhibitor of CDK2 significantly sensitize three subtypes of AML cells (including two non-APL cells) to ATRA-induced cell differentiation. Tretinoin 171-175 cyclin dependent kinase 2 Homo sapiens 81-85 31740384-8 2020 Thus, our work not only provides relevant experimental evidence for further validating CDK2 as a target for differentiation therapy, but also uncovers the future clinical application of CDK2 inhibitors in ATRA-based differentiation therapeutics for AML. Tretinoin 205-209 cyclin dependent kinase 2 Homo sapiens 87-91 31740384-8 2020 Thus, our work not only provides relevant experimental evidence for further validating CDK2 as a target for differentiation therapy, but also uncovers the future clinical application of CDK2 inhibitors in ATRA-based differentiation therapeutics for AML. Tretinoin 205-209 cyclin dependent kinase 2 Homo sapiens 186-190 30859584-4 2019 Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. Tretinoin 164-166 cyclin dependent kinase 2 Homo sapiens 125-129 24646031-3 2014 In many cases, downregulation of CDK activity by ATRA and vitamin D3 is a result of elevated p21- and p27-bound CDKs. Tretinoin 49-53 cyclin dependent kinase 2 Homo sapiens 112-116 30859584-4 2019 Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. Tretinoin 164-166 cyclin dependent kinase 2 Homo sapiens 98-123 28412739-7 2017 The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Tretinoin 49-62 cyclin dependent kinase 2 Homo sapiens 120-128 24646031-6 2014 ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 59-63 24646031-6 2014 ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 76-80 24646031-9 2014 Finally, sharp reduction in c-Myc has been observed in several leukaemia cell lines treated with ATRA, which may regulate expression of CDKs and CKIs. Tretinoin 97-101 cyclin dependent kinase 2 Homo sapiens 136-140 24635079-8 2014 ATRA also induced G1 cell-cycle arrest, inhibited the expression of cyclin D1/cyclin-dependent kinase (CDK)4 and cyclinE/CDK2, and increased the expression of the cyclin-dependent kinase inhibitors p21 and p27. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 121-125