Serum-Nutrient Starvation Induces Cell Death Mediated by Bax and Puma That Is Counteracted by p21 and Unmasked by Bcl-xL Inhibition 英文参考文献.docVIP

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Serum-Nutrient Starvation Induces Cell Death Mediated by Bax and Puma That Is Counteracted by p21 and Unmasked by Bcl-xL Inhibition 英文参考文献.doc

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Serum-Nutrient Starvation Induces Cell Death Mediated by Bax and Puma That Is Counteracted by p21 and Unmasked by Bcl-xL Inhibition 英文参考文献

Serum-NutrientStarvationInducesCellDeathMediated byBaxandPumaThatIsCounteractedbyp21and UnmaskedbyBcl-xLInhibition Fre′de′riqueBraun*,Jose′phineBertin-Ciftci,Anne-SophieGallouet,JulieMillour,PhilippeJuin* Institut deRechercheThe′rapeutique del’Universite′ deNantes,CentredeRechercheen Cance′rologie NantesAngers,Institut NationaldelaSante′ etdelaRecherche Me′dicaleUMR892/Universite′ deNantes,Nantes,France Abstract Thecyclin-dependentkinaseinhibitorp21(p21WAF1/Cip1)isamultifunctionalproteinknowntopromotecellcyclearrest andsurvivalinresponsetop53-dependentandp53independentstimuli.Wehereininvestigatedwhetherandhowitmight contributetothesurvivalofcancercellsthatareinlow-nutrientconditionsduringtumourgrowth,byculturingisogenic humancolorectalcancercelllines(HCT116)andbreastcancercelllinesinamediumdeprivedinaminoacidsandserum.We showthatsuchstarvationenhances,independentlyfromp53,theexpressionofp21andthatofthepro-apoptoticBH3-only protein Puma. Under these conditions, p21 prevents Puma and its downstream effector Bax from triggering the mitochondrialapoptoticpathway.Thisanti-apoptoticeffectisexertedfromthecytosolbutitisunrelatedtotheabilityof p21 to interfere with the effector caspase 3. The survival function of p21 is, however, overcome by RNA interference mediatedBcl-xLdepletion,orbythepharmacologicalinhibitorABT-737.Thus,aninsufficientsupplyinnutrientsmaynot haveanoverteffectoncancercellviabilityduetop21induction,butitprimesthesecellstodie,andsensitizesthemtothe deleteriouseffectsofBcl-xLinhibitorsregardlessoftheirp53status. Citation: Braun F, Bertin-Ciftci J, Gallouet A-S, Millour J, Juin P (2011) Serum-Nutrient Starvation Induces Cell Death Mediated by Bax and Puma That Is Counteractedbyp21andUnmaskedbyBcl-xLInhibition.PLoSONE6(8):e23577.doi:10.1371/journal.pone.0023577 Editor:AndreiL.Gartel,UniversityofIllinoisatChicago,UnitedStatesofAmerica ReceivedMarch28,2011;AcceptedJuly20,2011;PublishedAugust24,2011 Copyright: ? 2011 Braun et al. This is an open-access ar