Genomes and Genes
cyclin dependent kinase inhibitor p27
Summary: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
- Tiroch K, Koch W, Mehilli J, Bottiger C, Schomig A, Kastrati A. P27 and P53 gene polymorphisms and restenosis following coronary implantation of drug-eluting stents. Cardiology. 2009;112:263-9 pubmed publisher..This study could not demonstrate a clinically relevant role of P27 and P53 polymorphisms in the processes leading to in-stent restenosis. ..
- Nakamura T, Toita H, Yoshimoto A, Nishimura D, Takagi T, Ogawa T, et al. Potential involvement of Twist2 and Erk in the regulation of osteoblastogenesis by HB-EGF-EGFR signaling. Cell Struct Funct. 2010;35:53-61 pubmed..These results suggest that HB-EGF-EGFR signaling inhibits the differentiation of osteoblasts by suppression of Runx2 transcriptional activity and enhances proliferation of preosteoblasts by downregulation of expression of p27. ..
- Lee I, Yeom S, Lee S, Kang W, Park C. A novel senescence-evasion mechanism involving Grap2 and Cyclin D interacting protein inactivation by Ras associated with diabetes in cancer cells under doxorubicin treatment. Cancer Res. 2010;70:4357-65 pubmed publisher..0064). Therefore, we propose for the first time that Rad may promote carcinogenesis at least in part by inhibiting GCIP-mediated tumor suppression. ..
- Dozio E, Ruscica M, Passafaro L, Dogliotti G, Steffani L, Marthyn P, et al. The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells. Eur J Pharmacol. 2010;641:29-34 pubmed publisher..Thus, the anti-tumor activity of alpha-lipoic acid observed in MCF-7 cells further stresses the role of redox state in regulating cancer initiation and progression. ..
- Murato Y, Hashimoto C. Xhairy2 functions in Xenopus lens development by regulating p27(xic1) expression. Dev Dyn. 2009;238:2179-92 pubmed publisher..Based on these findings, we propose that Xhairy2 may maintain an intracellular environment in which inducing signal(s) can be accepted. ..
- Wang H, Bauzon F, Ji P, Xu X, Sun D, Locker J, et al. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. Nat Genet. 2010;42:83-8 pubmed publisher..These results reveal that Skp2 becomes an essential survival gene when susceptible cells incur Rb1 deficiency. ..
- Cova E, Ghiroldi A, Guareschi S, Mazzini G, Gagliardi S, Davin A, et al. G93A SOD1 alters cell cycle in a cellular model of Amyotrophic Lateral Sclerosis. Cell Signal. 2010;22:1477-84 pubmed publisher..As previously described in post mitotic neurons, cell cycle alterations could fatally lead to cell death. ..
- Ahn J, Hong S, Lee S, Kim J, Oh Y, Park S, et al. Cytoplasmic localization of Jab1 and p27 Kip1 might be associated with invasiveness of papillary thyroid carcinoma. Endocr J. 2009;56:707-13 pubmed
- Molatore S, Pellegata N. The MENX syndrome and p27: relationships with multiple endocrine neoplasia. Prog Brain Res. 2010;182:295-320 pubmed publisher..These findings are placed in the broader context of how p27 dysregulation might affect neuroendocrine cell function and trigger tumorigenesis...
- Sun Y, Zhao S, Tian H, Xie X, Xiao F, Li K, et al. Depletion of PI3K p85alpha induces cell cycle arrest and apoptosis in colorectal cancer cells. Oncol Rep. 2009;22:1435-41 pubmed..Activation of FoxO transcription factors also increased the expression of FasL. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p85alpha may be a useful therapeutic strategy for colorectal carcinoma. ..
- Trotman L, Niki M, Dotan Z, Koutcher J, Di Cristofano A, Xiao A, et al. Pten dose dictates cancer progression in the prostate. PLoS Biol. 2003;1:E59 pubmed..Our results provide conclusive genetic support for the notion that PTEN is haploinsufficient in tumor suppression and that its dose is a key determinant in cancer progression. ..
- Pascreau G, Eckerdt F, Churchill M, Maller J. Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding. Proc Natl Acad Sci U S A. 2010;107:2932-7 pubmed publisher..These results indicate that the cyclin A CLS may contribute to targeting and recognition of centrosomal Cdk substrates and is required for specific effects of p27(KIP1) on cyclin A-Cdk2. ..
- Flores O, Wang Z, Knudsen K, Burnstein K. Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition. Endocrinology. 2010;151:896-908 pubmed publisher..These data establish central roles for CDK2 nuclear-cytoplasmic trafficking and cyclin E in the mechanism of 1,25-(OH)(2)D(3)-mediated growth inhibition in prostate cancer cells. ..
- Welford S, Dorie M, Li X, Haase V, Giaccia A. Renal oxygenation suppresses VHL loss-induced senescence that is caused by increased sensitivity to oxidative stress. Mol Cell Biol. 2010;30:4595-603 pubmed publisher..Together, these data demonstrate that in vivo oxygenation promotes tolerance of VHL loss in renal epithelia, which may promote the development of renal carcinoma. ..
- Samba Louaka A, Taïeb F, Nougayrede J, Oswald E. Cif type III effector protein: a smart hijacker of the host cell cycle. Future Microbiol. 2009;4:867-77 pubmed publisher..This review summarizes and discusses what we know about Cif, from the bacterial gene to the host target. ..
- Chen J, Amos C, Merriman K, Wei Q, Sen S, Killary A, et al. Genetic variants of p21 and p27 and pancreatic cancer risk in non-Hispanic Whites: a case-control study. Pancreas. 2010;39:1-4 pubmed publisher..These results indicate that the p21 polymorphism may contribute to susceptibility to pancreatic cancer, particularly among p27 homozygous wild-type carriers and nonsmokers. ..
- Tosca L, Rame C, Chabrolle C, Tesseraud S, Dupont J. Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells. Reproduction. 2010;139:409-18 pubmed publisher..Taken together, our results strongly suggest that metformin reduces cell growth, protein synthesis, MAPK3/1, and P90RSK phosphorylation in response to IGF1 through an AMPK-dependent mechanism in cultured bovine granulosa cells. ..
- Zhou C, Xiang M, He S, Qian Z. Crocetin inhibits cell cycle G1/S transition through suppressing cyclin D1 and elevating p27kip1 in vascular smooth muscle cells. Phytother Res. 2010;24:975-81 pubmed publisher..In conclusion, our present results suggest that the inhibition of cell cycle G(1)/S transition in VSMCs by crocetin can be attributed, at least in part, to its suppression of cyclin D1 and elevation of CDKI p27(kip1). ..
- Wang C, Huang J, Gao X, Li Y, Zhou S, Yan X, et al. Fangchinoline induced G1/S arrest by modulating expression of p27, PCNA, and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenograft. Biosci Biotechnol Biochem. 2010;74:488-93 pubmed..Taking all this together, it can be concluded that Fan is an effective anti-proliferative agent that modulates cell growth regulators in prostate cancer cells. ..
- Liu H, Huang P, Xu X, Liu J, Guo C. Anticancer effect of celecoxib via COX-2 dependent and independent mechanisms in human gastric cancers cells. Dig Dis Sci. 2009;54:1418-24 pubmed publisher..These data extend our knowledge on the effect and mechanisms of celecoxib-induced inhibition of gastric carcinoma cell growth. ..
- Reisinger U, Schwaiger S, Zeller I, Messner B, Stigler R, Wiedemann D, et al. Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts. Cardiovasc Res. 2009;82:542-9 pubmed publisher..Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease. ..
- Tsai C, Chiu S, Liu C, Sheu T, Hsieh C, Keng P, et al. Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression. Cell Cycle. 2009;8:2365-74 pubmed..These data suggest that cofilin expression and its regulation of p27(kip1) expression is important for the control of G(1) phase progression. ..
- Cantor J, Browne C, Ruppert R, Feral C, Fassler R, Rickert R, et al. CD98hc facilitates B cell proliferation and adaptive humoral immunity. Nat Immunol. 2009;10:412-9 pubmed publisher..Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates. ..
- Cornelissen B, Kersemans V, McLarty K, Tran L, Reilly R. 111In-labeled immunoconjugates (ICs) bispecific for the epidermal growth factor receptor (EGFR) and cyclin-dependent kinase inhibitor, p27Kip1. Cancer Biother Radiopharm. 2009;24:163-73 pubmed publisher..These ICs were internalized into BC cells expressing EGFR and HER2 and imported into the nucleus. Their decreased retention by cells with trastuzumab-modulated p27(Kip1) suggests that they may be useful for probing this CDKI by imaging. ..
- Lin H, Chen Z, Wang G, Nardella C, Lee S, Chan C, et al. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature. 2010;464:374-9 pubmed publisher..Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy. ..
- Bashir T, Pagan J, Busino L, Pagano M. Phosphorylation of Ser72 is dispensable for Skp2 assembly into an active SCF ubiquitin ligase and its subcellular localization. Cell Cycle. 2010;9:971-4 pubmed
- Liu Y, Elsawa S, Almada L. Primers on molecular pathways - cycling toward pancreatic cancer. Pancreatology. 2010;10:6-13 pubmed publisher..We pay particular attention to pancreatic adenocarcinoma, an aggressive tumor that has a 5-year survival rate of 3-5%, and is the fourth leading cause of cancer mortality in the US. and IAP. ..
- Cheng J, Wang Y, Ma Y, Chan B, Yang M, Liang A, et al. The mechanical stress-activated serum-, glucocorticoid-regulated kinase 1 contributes to neointima formation in vein grafts. Circ Res. 2010;107:1265-74 pubmed publisher..However, it is unknown what intracellular growth signal leads to proliferation of venous SMCs...
- Pajalunga D, Puggioni E, Mazzola A, Leva V, Montecucco A, Crescenzi M. DNA replication is intrinsically hindered in terminally differentiated myotubes. PLoS ONE. 2010;5:e11559 pubmed publisher..Furthermore, this trait might contribute to explain the inability of these cells to play a role in tissue repair, unlike their counterparts in extensively regenerating species. ..
- Larocque D, Fragoso G, Huang J, Mushynski W, Loignon M, Richard S, et al. The QKI-6 and QKI-7 RNA binding proteins block proliferation and promote Schwann cell myelination. PLoS ONE. 2009;4:e5867 pubmed publisher..Our findings suggest that the QKI-6 and QKI-7 RNA binding proteins are positive regulators of PNS myelination and show that the QKI RNA binding proteins play a key role in Schwann cell differentiation and myelination. ..
- TSAI S, Hollenbeck S, Ryer E, Edlin R, Yamanouchi D, Kundi R, et al. TGF-beta through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation. Am J Physiol Heart Circ Physiol. 2009;297:H540-9 pubmed publisher..In the presence of elevated levels of Smad3 that develop in response to injury, TGF-beta stimulates smooth muscle cell proliferation through a mechanism involving the phosphorylation and nuclear export of p27. ..
- Sarfraz S, Hamid S, Ali S, Jafri W, Siddiqui A. Modulations of cell cycle checkpoints during HCV associated disease. BMC Infect Dis. 2009;9:125 pubmed publisher..The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development. ..
- Wolowiec D, Wojtowicz M, Ciszak L, Kosmaczewska A, Frydecka I, Potoczek S, et al. High intracellular content of cyclin-dependent kinase inhibitor p27(Kip1) in early- and intermediate stage B-cell chronic lymphocytic leukemia lymphocytes predicts rapid progression of the disease. Eur J Haematol. 2009;82:260-6 pubmed publisher..Our results indicate that elevated intracellular p27(Kip1) level in leukemic lymphocytes of early- and intermediate stage B-CLL patients contributes to rapid progression of the disease. ..
- Hammoud L, Burger D, Lu X, Feng Q. Tissue inhibitor of metalloproteinase-3 inhibits neonatal mouse cardiomyocyte proliferation via EGFR/JNK/SP-1 signaling. Am J Physiol Cell Physiol. 2009;296:C735-45 pubmed publisher..We conclude that TIMP-3 inhibits neonatal mouse cardiomyocyte proliferation by upregulating p27 expression. The effects of TIMP-3 are mediated via inhibition of EGFR expression/phosphorylation, and decreases in JNK and SP-1 signaling. ..
- Katakura M, Hashimoto M, Shahdat H, Gamoh S, Okui T, Matsuzaki K, et al. Docosahexaenoic acid promotes neuronal differentiation by regulating basic helix-loop-helix transcription factors and cell cycle in neural stem cells. Neuroscience. 2009;160:651-60 pubmed publisher..We therefore speculate that DHA is one of the essential key molecules for neuronal differentiation of NSCs. ..
- Lee S, Elphick L, Anderson A, Bonnac L, Child E, Mann D, et al. Synthesis and reactivity of novel gamma-phosphate modified ATP analogues. Bioorg Med Chem Lett. 2009;19:3804-7 pubmed publisher..g., click chemistry, Staudinger ligations). A preliminary screen of these compounds as phosphate donors with a typical wild type protein kinase (cdk2) and one of its known substrates p27(kip1) is also presented. ..
- Wurz K, Garcia R, Goff B, Mitchell P, Lee J, Tewari M, et al. MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival. Genes Chromosomes Cancer. 2010;49:577-84 pubmed publisher..01). In contrast, CDKN1B expression was not associated with miR-221 or miR-222 expression. Neither somatic mutations nor methylation of the studied region explained the alterations in miR-221 and miR-222 expression in most carcinomas. ..
- Huang C, Lin C, Huang H, Liu H, Chen Y, Shih D, et al. CKS1B overexpression implicates clinical aggressiveness of hepatocellular carcinomas but not p27(Kip1) protein turnover: an independent prognosticator with potential p27 (Kip1)-independent oncogenic attributes?. Ann Surg Oncol. 2010;17:907-22 pubmed publisher..The combined assessment of CKS1B and p27(Kip1) immunoexpressions effectively risk-stratifies HCCs with different prognoses, which may aid in the management of this deadly malignancy. ..
- Tang X, Vivero M, Gudas L. Overexpression of CRABPI in suprabasal keratinocytes enhances the proliferation of epidermal basal keratinocytes in mouse skin topically treated with all-trans retinoic acid. Exp Cell Res. 2008;314:38-51 pubmed
- Castro C, Lorenzo A, Gonzalez A, Cruzado M. Garlic components inhibit angiotensin II-induced cell-cycle progression and migration: Involvement of cell-cycle inhibitor p27(Kip1) and mitogen-activated protein kinase. Mol Nutr Food Res. 2010;54:781-7 pubmed publisher..Our findings show that AMS and DAS, compounds derivate from garlic, could be effective antioxidants targeted at the arterial remodelling seen in hypertension. ..
- Seluanov A, Hine C, Azpurua J, Feigenson M, Bozzella M, Mao Z, et al. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. Proc Natl Acad Sci U S A. 2009;106:19352-7 pubmed publisher..We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat...
- Miyake M, Ishii M, Koyama N, Kawashima K, Kodama T, Anai S, et al. 1-tert-butyl-3-[6-(3,5-dimethoxy-phenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea (PD173074), a selective tyrosine kinase inhibitor of fibroblast growth factor receptor-3 (FGFR3), inhibits cell proliferation of bladder cancer c. J Pharmacol Exp Ther. 2010;332:795-802 pubmed publisher
- Zhou W, Yang Q, Low C, Karthik B, Wang Y, Ryo A, et al. Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process. J Biol Chem. 2009;284:23980-8 pubmed publisher..Our study thus reveals a novel regulatory mechanism for p27(Kip1) stability and sheds new light on the biological function of Pin1 as a general regulator of protein stability. ..
- Chen J, Ding W, Xu S, Wang J, Huang Y, Deng C. Effect of p27mt gene on apoptosis of the colorectal cancer cell line Lovo. World J Gastroenterol. 2009;15:2794-9 pubmed..p27mt has an obvious blocking effect on colorectal cancer cell cycle, and most cells were inhibited in phase G(0)/G(1). Therefore, p27mt can induce apoptosis in colorectal cells. ..
- Shyla A, Hölzlwimmer G, Calzada Wack J, Bink K, Tischenko O, Guilly M, et al. Allelic loss of chromosomes 8 and 19 in MENX-associated rat pheochromocytoma. Int J Cancer. 2010;126:2362-72 pubmed publisher..Because of the high concordance of affected loci between rat and human tumors, studies of the MENX-associated pheochromocytomas should facilitate the identification of novel candidate genes implicated in their human counterpart. ..
- Stoppoloni D, Canino C, Cardillo I, Verdina A, Baldi A, Sacchi A, et al. Synergistic effect of gefitinib and rofecoxib in mesothelioma cells. Mol Cancer. 2010;9:27 pubmed publisher..Total EGFR expression and downstream signalling does not correlate with gefitinib sensitivity. These data suggest that the effect of gefitinib can be potentiated by rofecoxib in MM cell lines where AKT is not activated. ..
- Ramathal C, Bagchi I, Bagchi M. Lack of CCAAT enhancer binding protein beta (C/EBPbeta) in uterine epithelial cells impairs estrogen-induced DNA replication, induces DNA damage response pathways, and promotes apoptosis. Mol Cell Biol. 2010;30:1607-19 pubmed publisher..C/EBPbeta, therefore, is an essential mediator of E-induced growth and survival of uterine epithelial cells of cycling mice. ..
- Sredni S, Bonaldo M, Costa F, Huang C, Hamm C, Rajaram V, et al. Upregulation of mir-221 and mir-222 in atypical teratoid/rhabdoid tumors: potential therapeutic targets. Childs Nerv Syst. 2010;26:279-83 pubmed publisher..As anti-miR therapy was recently proposed as an alternative treatment for cancer, these findings suggest that anti-miR-221/222 therapy might have therapeutic potential in ATRT. ..