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Gene Review

Cdkn1b  -  cyclin-dependent kinase inhibitor 1B

Rattus norvegicus

Synonyms: CDKN4, Cdki1b, Kip1, P27KIP1, p27
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Disease relevance of Cdkn1b


Psychiatry related information on Cdkn1b


High impact information on Cdkn1b

  • Ectopic overexpression of p27 in serum-stimulated VSMCs resulted in the inhibition of cdk2 activity and repression of cyclin A promoter activity [7].
  • Using the rat carotid model of balloon angioplasty, a marked upregulation of p27 was observed in injured arteries [7].
  • High levels of p27 expression in the media and neointima correlated with downregulation of cdk2 activity at 2 wk after angioplasty, and adenovirus-mediated overexpression of p27 in balloon-injured arteries attenuated neointimal lesion formation [7].
  • p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis [8].
  • The activity of the cyclin-dependent kinase inhibitor p27 is controlled by its concentration and subcellular localization [8].

Biological context of Cdkn1b

  • Specific degradation of p27 by co-expressing Skp2 or p27 small interfering RNA caused an increase of CDK2 activity and overrode the limited cell cycle [9].
  • Co-treatment of cells with SMV (1 microM) inhibited Ang II-induced upregulation of p27 protein [10].
  • To delineate the molecular mechanism underlying the p27 down-regulation, we examined the effect of PDGF-BB on p27 promoter activity as well as mRNA stability [11].
  • The 1.04-kb cDNA of rat p27 contained an open reading frame of 197 amino acids that shared high homology with mammalian p27 and significant homology with mammalian p21Cip1 and p57Kip2. p27 mRNA was detected in most rat tissues and cell lines [12].
  • Both S phase entry and activation of cyclin/CDKs were inhibited by over expression of p27 [13].

Anatomical context of Cdkn1b

  • Biochemical analysis demonstrated that Skp2-dependent p27 ubiquitylation was remarkably suppressed in cardiomyocytes, whereas Skp2, a component of Skp1-Cullin-F-box protein ubiquitin ligase, was more actively ubiquitylated compared with proliferating rat fibroblasts [9].
  • Ang II (100 nM) stimulation of rat mesangial cells induced a significant increase in p27 protein expression [10].
  • In summary, our data suggest that p27 is down-regulated by PDGF-BB in vascular smooth muscle cells through an ERK-dependent posttranscriptional mechanism [11].
  • In this study, we show in rat aortic smooth muscle cells that PDGF-BB down-regulated p27 protein and mRNA in an ERK-dependent mechanism [11].
  • Posttranscriptional regulation of p18 and p27 Cdk inhibitor proteins and the timing of oligodendrocyte differentiation [14].

Associations of Cdkn1b with chemical compounds

  • Interestingly, leptomycin B-mediated nuclear accumulation accelerates the turnover of endogenous p27; the p27(S10A) mutant, which is trapped in the nucleus, has a shorter half-life than wild-type p27 and the p27(S10D) mutant [8].
  • Addition of mevalonate (200 microM) or geranylgeranyl pyrophosphate (5 microM) reversed the inhibitory effect of SMV on p27 protein expression, suggesting that the effect of SMV is geranylgeranyl dependent [10].
  • Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27 [10].
  • By contrast, we show that the overexpression of either p18 or p27 in OPCs proliferating in PDGF and the absence of TH greatly slows the cell cycle but fails to accelerate the spontaneous differentiation that normally occurs independently of TH [14].
  • In addition, H(2)O(2) caused a dramatic increase in expression of the cell cycle inhibitor p21 mRNA (9.67 +/- 0.94-fold at 2 h) and protein (8.75 +/- 0.08-fold at 8 h), but no change in p27 protein [15].

Physical interactions of Cdkn1b

  • The p27 complexed with Cdk2 dissociated after 2 days, whereas p21 associated in a reverse fashion [16].

Regulatory relationships of Cdkn1b


Other interactions of Cdkn1b

  • Decreased p27 was correlated with increased levels of Cdk2 and increased levels of phosphorylated retinoblastoma protein [19].
  • Basic fibroblast growth factor exhibits dual and rapid regulation of cyclin D1 and p27 to stimulate proliferation of rat cerebral cortical precursors [20].
  • Reduction in cell cycle kinase inhibitors p21 and p27 may contribute to activation of growth induced by in vivo AT(1) receptor stimulation [21].
  • Regulation of G(1) cyclin-dependent kinases in the liver: role of nuclear localization and p27 sequestration [22].
  • This response paralleled a loss of EGF-stimulated cdk2 kinase activity and an increase in association of the inhibitors p21 (cip-1) and p27 (kip-1) with cdk2 [23].

Analytical, diagnostic and therapeutic context of Cdkn1b

  • Thus, the inhibition of cdk2 function and repression of cyclin A gene transcription through the induction of the endogenous p27 protein provides a mechanism for the inhibition of VSMC growth at late time points after angioplasty [7].
  • However, the Cdk inhibitors p21 and p27 were up-regulated after treatment with tolbutamide and dbcAMP, suggesting that they would be involved in the decrease in pRb phosphorylation [2].
  • Flow cytometry analysis detected an increase in the percentage of cells involved in the S phase of the cycle, which correlated with increases in the levels of cyclins D1 and E (two G1-progression regulators), as well as in those of PCNA (proliferating cell nuclear antigen), and without modification in p27, an inhibitory protein of CDKs [24].
  • METHODS: Protein expression of the cyclins (D-type and E), Cdks (Cdk2 and 4), and Cdk inhibitors (p21 and p27) was measured by Western blot after SHAM operation or PH in F344 rats [25].
  • In conclusion, sustained activation of p42/p44 MAPKs and Cdk2 along with overexpression of cyclins D1 and E and reduction of p15 and p27 cyclin inhibitors occurred early after pancreatectomy and are active factors involved in signaling that leads to pancreas regeneration [16].


  1. Reversal of renal fibrosis, inflammation, and glomerular hypertrophy by kallikrein gene delivery. Bledsoe, G., Shen, B., Yao, Y., Zhang, J.J., Chao, L., Chao, J. Hum. Gene Ther. (2006) [Pubmed]
  2. Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation. Sánchez-Alvarez, R., Paíno, T., Herrero-González, S., Medina, J.M., Tabernero, A. Glia (2006) [Pubmed]
  3. Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium. Lahav-Baratz, S., Ben-Izhak, O., Sabo, E., Ben-Eliezer, S., Lavie, O., Ishai, D., Ciechanover, A., Dirnfeld, M. Mol. Hum. Reprod. (2004) [Pubmed]
  4. Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis. Alisi, A., Demori, I., Spagnuolo, S., Pierantozzi, E., Fugassa, E., Leoni, S. Cell. Physiol. Biochem. (2005) [Pubmed]
  5. Regulation of cyclin dependent kinase inhibitor proteins during neonatal cerebella development. Watanabe, G., Pena, P., Shambaugh, G.E., Haines, G.K., Pestell, R.G. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  6. Expression of viral proteins in mammalian cells transformed by avian sarcoma viruses. Aupoix, M., Vigier, P. Int. J. Cancer (1976) [Pubmed]
  7. Downregulation of cyclin-dependent kinase 2 activity and cyclin A promoter activity in vascular smooth muscle cells by p27(KIP1), an inhibitor of neointima formation in the rat carotid artery. Chen, D., Krasinski, K., Sylvester, A., Chen, J., Nisen, P.D., Andrés, V. J. Clin. Invest. (1997) [Pubmed]
  8. p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis. Rodier, G., Montagnoli, A., Di Marcotullio, L., Coulombe, P., Draetta, G.F., Pagano, M., Meloche, S. EMBO J. (2001) [Pubmed]
  9. Down-regulation of p27Kip1 promotes cell proliferation of rat neonatal cardiomyocytes induced by nuclear expression of cyclin D1 and CDK4. Evidence for impaired Skp2-dependent degradation of p27 in terminal differentiation. Tamamori-Adachi, M., Hayashida, K., Nobori, K., Omizu, C., Yamada, K., Sakamoto, N., Kamura, T., Fukuda, K., Ogawa, S., Nakayama, K.I., Kitajima, S. J. Biol. Chem. (2004) [Pubmed]
  10. Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27. Zeng, L., Xu, H., Chew, T.L., Chisholm, R., Sadeghi, M.M., Kanwar, Y.S., Danesh, F.R. J. Am. Soc. Nephrol. (2004) [Pubmed]
  11. PDGF-BB regulates p27 expression through ERK-dependent RNA turn-over in vascular smooth muscle cells. Sakakibara, K., Kubota, K., Worku, B., Ryer, E.J., Miller, J.P., Koff, A., Kent, K.C., Liu, B. J. Biol. Chem. (2005) [Pubmed]
  12. Cloning and characterization of rat p27Kip1, a cyclin-dependent kinase inhibitor. Nomura, H., Sawada, Y., Fujinaga, K., Ohtaki, S. Gene (1997) [Pubmed]
  13. The mechanism of cell cycle regulation by v-Src. Riley, D., Carragher, N.O., Frame, M.C., Wyke, J.A. Oncogene (2001) [Pubmed]
  14. Posttranscriptional regulation of p18 and p27 Cdk inhibitor proteins and the timing of oligodendrocyte differentiation. Tokumoto, Y.M., Apperly, J.A., Gao, F.B., Raff, M.C. Dev. Biol. (2002) [Pubmed]
  15. Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle. Deshpande, N.N., Sorescu, D., Seshiah, P., Ushio-Fukai, M., Akers, M., Yin, Q., Griendling, K.K. Antioxid. Redox Signal. (2002) [Pubmed]
  16. Expression and modulation of p42/p44 MAPKs and cell cycle regulatory proteins in rat pancreas regeneration. Morisset, J., Aliaga, J.C., Calvo, E.L., Bourassa, J., Rivard, N. Am. J. Physiol. (1999) [Pubmed]
  17. A p160ROCK-specific inhibitor, Y-27632, attenuates rat hepatic stellate cell growth. Iwamoto, H., Nakamuta, M., Tada, S., Sugimoto, R., Enjoji, M., Nawata, H. J. Hepatol. (2000) [Pubmed]
  18. The induction of cell cycle regulatory and DNA repair proteins in cisplatin-induced acute renal failure. Zhou, H., Kato, A., Yasuda, H., Miyaji, T., Fujigaki, Y., Yamamoto, T., Yonemura, K., Hishida, A. Toxicol. Appl. Pharmacol. (2004) [Pubmed]
  19. Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation. Everly, D.N., Mainou, B.A., Raab-Traub, N. J. Virol. (2004) [Pubmed]
  20. Basic fibroblast growth factor exhibits dual and rapid regulation of cyclin D1 and p27 to stimulate proliferation of rat cerebral cortical precursors. Li, B., DiCicco-Bloom, E. Dev. Neurosci. (2004) [Pubmed]
  21. Expression of cell cycle proteins in blood vessels of angiotensin II-infused rats: role of AT(1) receptors. Diep, Q.N., El Mabrouk, M., Touyz, R.M., Schiffrin, E.L. Hypertension (2001) [Pubmed]
  22. Regulation of G(1) cyclin-dependent kinases in the liver: role of nuclear localization and p27 sequestration. Albrecht, J.H., Rieland, B.M., Nelsen, C.J., Ahonen, C.L. Am. J. Physiol. (1999) [Pubmed]
  23. Abbreviated cell cycle progression induced by the serine/threonine protein phosphatase inhibitor okadaic acid at concentrations that promote neoplastic transformation. Messner, D.J., Ao, P., Jagdale, A.B., Boynton, A.L. Carcinogenesis (2001) [Pubmed]
  24. Induction of cell proliferation by cyclosporine A in primary cultures of rat hepatocytes. Andrés, D., Díez-Fernández, C., Zaragoza, A., Alvarez, A., Cascales, M. Biochem. Pharmacol. (2001) [Pubmed]
  25. Cell cycle-mediated regulation of hepatic regeneration. Ehrenfried, J.A., Ko, T.C., Thompson, E.A., Evers, B.M. Surgery (1997) [Pubmed]
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