Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in Drosophila 英文参考文献.docVIP

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Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in Drosophila 英文参考文献.doc

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Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in Drosophila 英文参考文献

AntagonisticRegulationofApoptosisandDifferentiation bytheCutTranscriptionFactorRepresentsaTumor- SuppressingMechanisminDrosophila ZongzhaoZhai1,NatiHa1.,FaniPapagiannouli1.,AnneHamacher-Brady2.,NathanBrady2. ,Sebastian Sorge1,DanielaBezdan3,IngridLohmann1* 1CellNetworks–ClusterofExcellence,CentreforOrganismalStudies(COS)Heidelberg,UniversityofHeidelberg,Heidelberg,Germany,2GermanCancerResearchCenter (DKFZ),Heidelberg,Germany,3MaxPlanckInstituteforDevelopmentalBiology,Tu¨bingen,Germany Abstract Apoptosisisessentialtopreventoncogenictransformationbytriggeringself-destructionofharmfulcells,includingthose unabletodifferentiate.However,themechanismslinkingimpairedcelldifferentiationandapoptosisduringdevelopment and disease are not well understood. Here we report that the Drosophila transcription factor Cut coordinately controls differentiationandrepressionofapoptosisviadirectregulationofthepro-apoptoticgenereaper.Wealsodemonstratethat thisregulatorycircuitactsindiversecelllineagestoremoveuncommittedprecursorcellsinstatusnascendiandthereby interfereswiththeirpotentialtodevelopintocancercells.ConsistentwiththeroleofCuthomologuesincontrollingcell deathinvertebrates,wefindrepressionofapoptosisregulatorsbyCux1inhumancancercells.Finally,wepresentevidence that suggests that other lineage-restricted specification factors employ a similar mechanism to put the brakes on the oncogenicprocess. Citation: Zhai Z, Ha N, Papagiannouli F, Hamacher-Brady A, Brady N, et al. (2012) Antagonistic Regulation of Apoptosis and Differentiation by the Cut TranscriptionFactorRepresentsaTumor-SuppressingMechanisminDrosophila.PLoSGenet8(3):e1002582.doi:10.1371/journal.pgen.1002582 Editor:EricRulifson,UniversityofCaliforniaSanFrancisco,UnitedStatesofAmerica ReceivedOctober12,2011;AcceptedJanuary19,2012;PublishedMarch15,2012 Copyright:?2012Zhaietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymed