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S Phase–Coupled E2f1 Destruction Ensures Homeostasis in Proliferating Tissues 英文参考文献
SPhase–CoupledE2f1DestructionEnsuresHomeostasis
inProliferatingTissues
JeanM.Davidson1,RobertJ.Duronio1,2,3*
1DepartmentofBiology,TheUniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2LinebergerComprehensiveCancerCenter,
TheUniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3PrograminMolecularBiologyandBiotechnology,TheUniversityof
NorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica
Abstract
Precisecontrolofcellcycleregulatorsiscriticalfornormaldevelopmentandtissuehomeostasis.E2Ftranscriptionfactors
areactivatedduringG1todrivetheG1-StransitionandaretheninhibitedduringSphasebyavarietyofmechanisms.Here,
wegeneticallymanipulatethesingleDrosophilaactivatorE2F(E2f1)toexplorethedevelopmentalrequirementforSphase–
coupled E2F down-regulation. Expression of an E2f1 mutant that is not destroyed during S phase drives cell cycle
progression and causes apoptosis. Interestingly, this apoptosis is not exclusively the result of inappropriate cell cycle
progression,becauseastableE2f1mutantthatcannotfunctionasatranscriptionfactorordrivecellcycleprogressionalso
triggersapoptosis.ThisobservationsuggeststhattheinappropriatepresenceofE2f1proteinduringSphasecantrigger
apoptosisbymechanismsthatareindependentofE2Factingdirectlyattargetgenes.TheabilityofSphase-stabilizedE2f1
totriggerapoptosisrequiresaninteractionbetweenE2f1andtheDrosophilapRbhomolog,Rbf1,andinvolvesinductionof
the pro-apoptotic gene, hid. Simultaneously blocking E2f1 destruction during S phase and inhibiting the induction of
apoptosisresultsintissueovergrowthandlethality.WeproposethatinappropriateaccumulationofE2f1proteinduringS
phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of
rapidlyproliferatingtissues.
Citation: Davidson JM, Duronio RJ (2012) S Phase–Coupled E2f1 Destruction Ensures Homeostasis in Proliferating Tissues. PLoS Genet 8(8): e1002831.
doi:10.1371/jo
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