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EMBO J. 2012 Jun 29;31(13):2952-64. doi: 10.1038/emboj.2012.122. Epub 2012 May 8.

The p57 CDKi integrates stress signals into cell-cycle progression to promote cell survival upon stress.

Author information

1
Departament de Ciències Experimentals i de la Salut, Cell Signaling Research Group, Univeristat Pompeu Fabra, Barcelona, Spain. manel.joaquin@upf.edu

Abstract

The p57(Kip2) cyclin-dependent kinase inhibitor (CDKi) has been implicated in embryogenesis, stem-cell senescence and pathologies, but little is known of its role in cell cycle control. Here, we show that p57(Kip2) is targeted by the p38 stress-activated protein kinase (SAPK). Phosphorylation of p57(Kip2) at T143 by p38 enhances its association with and inhibition of Cdk2, which results in cell-cycle delay upon stress. Genetic inactivation of the SAPK or the CDKi abolishes cell-cycle delay upon osmostress and results in decreased cell viability. Oxidative stress and ionomycin also induce p38-mediated phosphorylation of p57 and cells lacking p38 or p57 display reduced viability to these stresses. Therefore, cell survival to various stresses depends on p57 phosphorylation by p38 that inhibits CDK activity. Together, these findings provide a novel molecular mechanism by which cells can delay cell cycle progression to maximize cell survival upon stress.

PMID:
22569127
PMCID:
PMC3395087
DOI:
10.1038/emboj.2012.122
[Indexed for MEDLINE]
Free PMC Article
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