分子细胞生物学前沿-博士

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1、分子细胞生物学专题----转录延伸因子P-TEFb及其活性调控生命科学学院陈瑞川细胞生物学博士研究生课程MainPointsTranscriptionprocessofeukaryoticgene.P-TEFb:functionsanditsActivityregulationI.TranscriptionprocessStepsofclassIIgenetranscriptionPromotorclearenceInitiationPICassemblyTerminationElongationTFIIA,TFIIB,TFIID,TFIIE,TFII

2、F,andTFIIHRNApolymeraseII(PolII)TheclassIIpre-initiationcomplex(PIC)RNApolymeraseII(PolII)12subunites:Rpb1-Rpb12About500KdaofMWRpb1:largestsubunit,CTD:Y1S2P3T4S5P6S7Yest:26repeatsC.elegans:32repeatsDrosophila42repeatsMammals:52repeatsPre-initiationPolIICTDPICassemblyIIFIIHIIEPIC

3、PolIICTDIIFPolIICTDIIFIIDIIAIIBIIHIIE+1DNAtempTATAPICPolIICTDIIDIIAIIBIIFIIHIIEInitiation55555PolII55555+1DNAtempTATAPromoterclearance20-30ntPolIICTD55555DNAtempTATAIISDSIFNELFMTPausingCappingPolIICTD55555DNAtempTATAIISRNADSIFNELFEarlyelongation5'-triphosphataseguanyltransferase

4、NCNCmethyltransferaseMTMTNCNCCappingEarlyelongationDNAtempProductiveElongationCycT1CDK9P-TEFbRNACycT1CDK9P-TEFbPolIICTD55555IISDSIF2222CycT1CDK9P-TEFbNELFPolIICTD55555IISDSIFCappedshortmRNA2222PPCycT1CDK9P-TEFbSplicing55555PolII22222RNADNAtempRNAUsnRNPProductiveElongationSplicin

5、gCycT1CDK9P-TEFbFCP1PolIIPolIICTD25555222PolII25555222+15555PolII5’capRNA55552222PolIICTDTFIIHNFkBSp1NFATPolIISteps:Pre-initiationInitiationPromoterclearanceElongationTerminationInitiationEarlyelongationPromoterclearanceElongationTerminationPre-initiationTranscriptioncycleTransc

6、riptionProcessP-TEFb,itsfunctionsandactivityregulationP-TEFb:compositionandpropertyDiscoveredin1995.(positivetranscriptionelongationfactorb)AheterodimerofCdk9andcyclinT,includingT1,T2a,T2bandCyclinK.But80%P-TEFbisCDK9/CyclinT1.kinase,phosphorylatesCTDofPolII,DSIFandNELF.CycT1Cdk

7、9PhysiologicalfunctionsAglobaltranscriptionalelongationfactorEssentialformorethan80%mRNAtranscriptionEssentialforembryodevelopmentCTDPolIIRNANELFNuc失败转录CycT1Cdk9P-TEFb成功转录RNAPPPPPPPPCycT1Cdk9AdaptedafterPrice,MCB20:2629(2000)P-TEFb在基因转录过程中的作用机制——模式图B.PathologicalfunctionsExquisi

8、telyrequiredforHIV-1geneexpressionAbnormallyhig