Association of Tat with Promoters of PTEN and PP2A Subunits Is Key to Transcriptional Activation of Apoptotic Pathways in HIV-Infected CD4+ T Cells 英文参考文献.docVIP

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Association of Tat with Promoters of PTEN and PP2A Subunits Is Key to Transcriptional Activation of Apoptotic Pathways in HIV-Infected CD4+ T Cells 英文参考文献.doc

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AssociationofTatwithPromotersofPTENandPP2ASubunitsIsKeytoTranscriptionalActivationofApoptoticPathwaysinHIV-InfectedCD4TCells英文参考文献

AssociationofTatwithPromotersofPTENandPP2A SubunitsIsKeytoTranscriptionalActivationof ApoptoticPathwaysinHIV-InfectedCD4+TCells NayoungKim1,SamiKukkonen1,SumeetGupta2,AnnaAldovini1* 1Children’s Hospital Boston, Department of Medicine, and Harvard Medical School, Department of Pediatrics, Boston, Massachusetts, United States of America, 2WhiteheadInstituteforBiomedicalResearch,Cambridge,Massachusetts,UnitedStatesofAmerica Abstract Apoptosis in HIV-1-infected CD4+ primary T cells is triggered by the alteration of the PI3K and p53 pathways, which convergeontheFOXO3atranscriptionalactivator.TatalonecancauseactivationofFOXO3aandofitsproapoptotictarget genes.TounderstandhowTataffectsthispathway,wecarriedoutChIP-ChipexperimentswithTat.Tatassociateswiththe promotersofPTENandtwoPP2Asubunitgenes,butnotwiththeFOXO3apromoter.PTENandPP2Aencodephosphatases, whoselevelsandactivityareincreasedwhenTatisexpressed.TheycounteractphosphorylationofAkt1andFOXO3a,and so activate transcriptional activity of FOXO3a. FOXO3a promotes increased transcription of Egr-1, which can further stimulatethetranscriptionofPTEN,therebyreinforcingthepathwaythatleadstoFOXO3atranscriptionalactivation.RNAi experimentssupporttheroleofPTENandPP2AintheinitiationoftheTat-mediatedcascade,whichiscriticaltoapoptosis. The increased accumulation of PTEN and PP2A subunit mRNAs during Tat expression is more likely to be the result of increasedtranscriptioninitiationandnotreliefofpromoter-proximalpausingofRNAPII.TheTat-PTENand-PP2Apromoter interactionsprovideamechanisticexplanationofTat-mediatedapoptosisinCD4+Tcells. Citation:KimN,KukkonenS,GuptaS,AldoviniA(2010)AssociationofTatwithPromotersofPTENandPP2ASubunitsIsKeytoTranscriptionalActivationof ApoptoticPathwaysinHIV-InfectedCD4+TCells.PLoSPathog6(9):e1001103.doi:10.1371/journal.ppat.1001103 Editor:AndrewP.Rice,BaylorCollegeofMedicine,UnitedStatesofAmerica ReceivedNovember3,2009;AcceptedAugust13,2010;PublishedSeptember16,2010 Copyright:?2010Kimetal.Thisisanopen-access