E2F and p53 Induce Apoptosis Independently during Drosophila Development but Intersect in the Context of DNA Damage 英文参考文献.docVIP

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E2F and p53 Induce Apoptosis Independently during Drosophila Development but Intersect in the Context of DNA Damage 英文参考文献.doc

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E2F and p53 Induce Apoptosis Independently during Drosophila Development but Intersect in the Context of DNA Damage 英文参考文献

E2Fandp53InduceApoptosisIndependentlyduring DrosophilaDevelopmentbutIntersectintheContextof DNADamage Nam-SungMoon1,2¤,LuisaDiStefano1,2,ErickJ.Morris1,2,ReenaPatel3,KristinWhite3,NicholasJ. Dyson1,2 * 1Massachusetts General Hospital Cancer Research Center, Charlestown, Massachusetts, United States of America, 2Harvard Medical School, Boston, Massachusetts, UnitedStatesofAmerica,3CutaneousBiologyResearchCenter,MassachusettsGeneralHospital,Charlestown,Massachusetts,UnitedStatesofAmerica Abstract In mammalian cells, RB/E2F and p53 are intimately connected, and crosstalk between these pathways is critical for the inductionofcellcyclearrestorcelldeathinresponsetocellularstresses.Herewehaveinvestigatedthegeneticinteractions between RBF/E2F and p53 pathways during Drosophila development. Unexpectedly, we find that the pro-apoptotic activities of E2F and p53 are independent of one another when examined in the context of Drosophila development: apoptosis induced by thederegulation of dE2F1,or by theoverexpression of dE2F1, is unaffected by the elimination of dp53;conversely,dp53-inducedphenotypesareunaffectedbytheeliminationofdE2Factivity.However,dE2Fanddp53 convergeinthecontextofaDNAdamageresponse.BothdE2F1/dDPanddp53arerequiredforDNAdamage-inducedcell death,andtheanalysisofrbf1mutanteyediscsindicatesthatdE2F1/dDPanddp53cooperativelypromotecelldeathin irradiateddiscs.Inthiscontext,thefurtherderegulationintheexpressionofpro-apoptoticgenesgeneratesanadditional sensitivitytoapoptosisthatrequiresbothdE2F/dDPanddp53activity.ThissensitivitydiffersfromDNAdamage-induced apoptosis in wild-type discs (and from dE2F/dDP-induced apoptosis in un-irradiated rbf1 mutant eye discs) by being dependent on both hid and reaper. These results show that pro-apoptotic activities of dE2F1 and dp53 are surprisingly separable:dp53isrequiredfordE2F-dependentapoptosisintheresponsetoDNAdamage,butitisnotrequiredfordE2F- dependentapoptosiscausedsimplybytheinactivationofrbf1. Citation:MoonN-S,DiStefan