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

The EMBO Journal
Manel JoaquinFrancesc Posas

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.

References

Aug 5, 1994·Science·Z Galcheva-GargovaR J Davis
Nov 15, 1995·Structure·N R BrownL N Johnson
Jun 13, 2001·American Journal of Physiology. Cell Physiology·D J ElziC C Silliman
Dec 4, 2001·Biology of the Cell·C Ambrosino, A R Nebreda
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Natalia I DmitrievaMaurice B Burg
Mar 13, 2002·The Journal of Biological Chemistry·Noriko IshidaKeiichi I Nakayama
Jun 12, 2002·The Journal of Biological Chemistry·Geum-Yi KimEileen Friedman
Aug 2, 2002·EMBO Reports·Eulàlia de NadalFrancesc Posas
Sep 24, 2002·Nature Medicine·Jiyong LiangJoyce M Slingerland
Dec 17, 2002·Molecular and Cellular Biology·Concetta AmbrosinoAngel R Nebreda
Mar 29, 2003·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Rajeshwar P Sinha, Donat P Häder
Aug 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Takumi KamuraKeiichi I Nakayama
Sep 28, 2004·Nature Cell Biology·Xavier EscotéFrancesc Posas
Nov 9, 2004·Advances in Cancer Research·Dmitry V Bulavin, Albert J Fornace
Oct 21, 2005·Trends in Biochemical Sciences·Marcos Malumbres, Mariano Barbacid
Oct 21, 2006·The EMBO Journal·Uta KossatzNisar P Malek
Feb 13, 2008·Developmental Cell·Arnaud BessonJames M Roberts
May 30, 2009·Molecular Biology of the Cell·Gilad YaakovFrancesc Posas
Oct 22, 2009·Cancer Research·Myriam CuadradoOscar Fernandez-Capetillo
Nov 26, 2009·Molecular Cancer Research : MCR·Ioannis S PaterasVassilis G Gorgoulis
Aug 6, 2011·Molecular Cancer Research : MCR·Adriana BorrielloFulvio Della Ragione
Sep 3, 2011·Cell Stem Cell·Melania Tesio, Andreas Trumpp
Sep 3, 2011·Cell Stem Cell·Akinobu MatsumotoKeiichi I Nakayama

❮ Previous
Next ❯

Citations

Feb 2, 2013·Drugs·Verica Paunovic, Margaret M Harnett
Oct 3, 2012·Genetics·Haruo Saito, Francesc Posas
Aug 3, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·José Manuel Pérez MartínMaría José Hazen
Sep 18, 2014·Science Signaling·Jay L Brewster, Michael C Gustin
Jul 23, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Yanshu LiFeng Li
Oct 23, 2015·Mediators of Inflammation·Marianna Nicoletta Rossi, Fabrizio Antonangeli
May 27, 2014·Cancer Cell International·Abdelkader HamadiPhilippe Rondé
Apr 1, 2015·The Journal of Experimental Medicine·Melania TesioAndreas Trumpp
Sep 12, 2013·Journal of Molecular Biology·Alba DuchFrancesc Posas
Jun 22, 2018·Oncology Letters·Tai Ping ZhaoYi Min Han
Jul 13, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eduardo PaulsJosé A Esté
Feb 14, 2020·International Journal of Molecular Sciences·Emanuela StamponeAdriana Borriello
Mar 15, 2020·International Journal of Molecular Sciences·Adrián Martínez-LimónEulàlia de Nadal
Feb 16, 2017·Molecular & Cellular Oncology·Manel JoaquinFrancesc Posas
Oct 22, 2019·Frontiers in Cell and Developmental Biology·Michael Jeremy ShapiroVirginia Smith Shapiro
Sep 17, 2020·Biomolecules·Gian Luigi RussoAdriana Borriello
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Justine Creff, Arnaud Besson

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
FACS
transfection
transfections
PCR

Software Mentioned

ImageQuant
CellQuest
WinMDI

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.