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

Joaquin i Caudet, Manel; Gubern, Albert; González Nuñez, Daniel; Ruiz, E. Josué; Ferreiro Neira, Isabel; Nadal Clanchet, Eulàlia de; Nebreda, Ángel R.; Posas Garriga, Francesc

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

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dc.contributor.author Joaquin i Caudet, Manelca
dc.contributor.author Gubern, Albertca
dc.contributor.author González Nuñez, Danielca
dc.contributor.author Ruiz, E. Josuéca
dc.contributor.author Ferreiro Neira, Isabelca
dc.contributor.author Nadal Clanchet, Eulàlia deca
dc.contributor.author Nebreda, Ángel R.ca
dc.contributor.author Posas Garriga, Francescca
dc.date.accessioned 2015-12-09T13:38:16Z
dc.date.available 2015-12-09T13:38:16Z
dc.date.issued 2012
dc.description.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.ca
dc.description.sponsorship This work was supported by the MICINN grant BFU2007-66503 and BFU2010-15839 to M Joaquin and BIO2009-07762, Consolider Ingenio 2010 programme (grant CSD2007-0015) and through contract No. ERAS-CT-2003-980409 of the European Commission, DG Research, FP6 as part of an EURYIscheme award and the Fundación Marcelino Botín to F Posas. F Posas and E de Nadal are recipient of an ICREA Acadèmia (Generalitat de Catalunya)
dc.format.mimetype application/pdfca
dc.identifier.citation Joaquin M, Gubern A, González-Nuñez D, Josué Ruiz E, Ferreiro I, de Nadal E et al. The p57 CDKi integrates stress signals into cell-cycle progression to promote cell survival upon stress. EMBO journal. 2012;31(13):2952-64. DOI: 10.1038/emboj.2012.122ca
dc.identifier.doi http://dx.doi.org/10.1038/emboj.2012.122
dc.identifier.issn 0261-4189
dc.identifier.uri http://hdl.handle.net/10230/25353
dc.language.iso engca
dc.publisher Nature Publishing Groupca
dc.relation.ispartof EMBO journal. 2012;31(13):2952-64
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BFU2007-66503
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-15839
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2009-07762
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/980409
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/ca
dc.subject.keyword Cell cycle
dc.subject.keyword Cell stress
dc.subject.keyword Cell survival
dc.subject.keyword p38 SAPK
dc.subject.keyword p57 CDKi
dc.subject.other Osmosica
dc.subject.other Estrès oxidatiu -- Fisiologia patològicaca
dc.subject.other Fosforilacióca
dc.title The p57 CDKi integrates stress signals into cell-cycle progression to promote cell survival upon stressca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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