ThecellcycletransitionfromG1toSphaseisakeyregulatorypointinthecellcycle.Thistransitionisregulatedbythecheckpointkinasecdk2thatactivatestheG1toStransitionwhenitisassociatedwithcyclinE.Cdk2/CyclinEcausestheG1toStransitionthroughphosphorylationofthetumorsuppressorRb,releasingthetranscriptionfactorE2F-1.OtherpathwaysactingthroughRac,RasandRhoalsoregulatetheG1toStransition.RasregulatescyclinD1expressiontoaffecttheG1toStransition.TransformingformsofRasorRafinducecyclinD1expressionandcauseearlyentryintoSphase.SignalingfromRastoRaftoMEKtoERKsinducesCyclinD1expression,allowingCyclinD1tocomplexwithCdk4andCdk6andphosphorylateRb.Rac-1andPAKappeartoinduceCyclinD1expressionandinducetheG1toStransitionprimarilythroughactivationofNF-kBtoactivatetheCyclinD1promoter.Rhoactivatescdk2andalsoinhibitsp21andp27toinducecyclinD1andstimulatetheG1toStransition.Rhorepressesp21expressiontoblockp21inductionbyRasandtoallowRasinducedprogressionfromG1toS.Cellsthatlackp21donotrequireRhoforRastoinducecellcycleprogressionfromG1toSphase.ThecooperativeactionofRas,RacandRhotoinduceCyclinD1expressionisakeycomponentofoncogenictransformation.

Contributor:

REFERENCES:Baldin,V.etal.(1993)CyclinD1isanuclearproteinrequiredforcellcycleprogressioninG1.GenesDev(5),812-21DafnaBar-SagiandAlanHall.(2000)RasandRhoGTPases:AFamilyReunion.Cell,Vol.103,227-238Frost,Jeffreyetal.(2000)StimulationofNFkBActivitybyMultipleSignalingPathwaysRequiresPAK1.J.BiolChem275(26):19693-99Guttridge,D.C.etal.(1999)NF-kappaBcontrolscellgrowthanddifferentiationthroughtranscriptionalregulationofcyclinD1.MolCellBiol19(8),5785-99Hirai,A.etal.(1997)GeranylgeranylatedrhosmallGTPase(s)areessentialforthedegradationofp27Kip1andfacilitatetheprogressionfromG1toSphaseingrowth-stimulatedratFRTL-5cells.JBiolChem.272(1),13-6.Kerkhoff,E.,Rapp,U.R.(1997)InductionofcellproliferationinquiescentNIH3T3cellsbyoncogenicc-Raf-1.MolCellBiol17(5),2576-86Liberto,M.,Cobrinik,D.,Minden,A.(2002)Rhoregulatesp21(CIP1),cyclinD1,andcheckpointcontrolinmammaryepithelialcells.Oncogene21(10),1590-9Tanaka,T.etal.(1998)Activationofcyclin-dependentkinase2(Cdk2)ingrowth-stimulatedratastrocytes.GeranylgeranylatedRhosmallGTPase(s)areessentialfortheinductionofcyclinEgeneexpression.JBiolChem.273(41),26772-8.Welsh,Catherineetal.(2001)TimingofcyclinD1expressionwithinG1phaseiscontrolledbyRho.NatureCellBiovol3;Nov2001:950-57

================  蚂蚁淘在线  ================

免责声明：本文仅代表作者个人观点，与本网无关。其创作性以及文中陈述文字和内容未经本站证实，对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不做任何保证或承诺，请读者仅作参考，并请自行核实相关内容

版权声明：未经蚂蚁淘在线授权不得转载、摘编或利用其他方式使用上述作品。已经经本网授权使用作品的，应该授权范围内使用，并注明“来源：蚂蚁淘在线”。违反上述声明者，本网将追究其相关法律责任。