Disease relevance of Cdkn1b

• Moreover, kallikrein reversed salt-induced glomerular hypertrophy and inhibited the increase in levels of the cell cycle-inhibitory proteins p21 and p27 [1].
• Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation [2].
• The expression of p27 in endometrial carcinoma is very low but has been found to increase following treatment with progesterone [3].
• Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27 [4].
• Protein-calorie malnutrition, which was previously shown to arrest rat cerebella development, reduced cyclin D1 kinase activity and p27 levels [5].

Psychiatry related information on Cdkn1b

• The failure of p27 to insert in the cell membrane could account for the low permissiveness or the non-permissiveness of the cells [6].

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

• This shape-dependent block in cell proliferation correlated with a failure to increase cyclin D1 protein level and to down-regulate the cell cycle inhibitor p27 [17].
• SA augmented CDDP-induced increment of p27 but suppressed the increased expression of cyclin B1 and cyclin D1 at 3 days after CDDP [18].

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].

References