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Regulation of cell cycle progression by Plk3
ThefocusofthispathwayistoillustratetheroleofPolo-likeKinase3(Plk3alsoknownasPrkandFnk)aspartoftheregulatorycascadeleADIngtoapoptosisandthearrestcellcycleprogressionpriortoMphase.PhosphorlyationofCdc25Conserine-216causesthearrestofthecellcycleattheG2/MphaseborderbypreventingCdc25CfromactivatingcyclinB1/Cdk1.Xieetal.demonstratedthatPlk3likeChk1andChk2alsophosphorlyatesCdc25Conserine-216contributingtocellcyclearrest.AdditionallytheyfoundthatPlk3alsophosphorylatesp53onserine20atstepthatisstimulatoryintheprocessleadinguptop53-mediatedapoptosis.WangQetal.foundthatPlk3iscloselyassociatedwiththecentrosomeandthatthiswasdependentontheintegrityofthemicrotubules.ExpressionofconstitutivelyactiveordefectivePlk3kinasehadsignificantdefectsontheshapeandnatureofthemicrotubuleapparatusofthecell.Ineithercasecellcycleprogressionwashaltedandapoptosisoccurred. Contributor:KosiGramatikoff,PhD REFERENCES:BulavinDV,AmundsonSA,FornaceAJ.p38andChk1kinases:differentconductorsfortheG(2)/Mcheckpointsymphony.CurrOpinGenetDev.2002Feb;12(1):92-7.DemingPB,CistulliCA,ZhaoH,GravesPR,Piwnica-WormsH,PaulesRS,DownesCS,KaufmannWK.Thehumandecatenationcheckpoint.ProcNatlAcadSciUSA.2001Oct9;98(21):12044-9.HuB,ZhouXY,WangX,ZengZC,IliakisG,WangY.TheradioresistancetokillingofA1-5cellsderivesfromactivationoftheChk1pathway.JBiolChem.2001May25;276(21):17693-8.LiuHY,NefskyBS,WalworthNC.TheDed1DEADboxhelicaseinteractswithChk1andCdc2.JBiolChem.2002Jan25;277(4):2637-43.MihaylovIS,KondoT,JonesL,RyzhikovS,TanakaJ,ZhengJ,HigaLA,MinaminoN,CooleyL,ZhangH.ControlofDNAreplicationandchromosomeploidybygemininandcyclinA.MolCellBiol.2002Mar;22(6):1868-80.ONeillT,GiarrataniL,ChenP,IyerL,LeeCH,BobiakM,KanaiF,ZhouBB,ChungJH,RathbunGA.DeterminationofsubstratemotifsforhumanChk1andhCds1/Chk2bytheorientedpeptidelibraryapproach.JBiolChem.2002May3;277(18):16102-15.SavitskyPA,FinkelT.RedoxregulationofCdc25C.JBiolChem.2002Jun7;277(23):20535-40.WangQ,XieS,ChenJ,FukasawaK,NaikU,TraganosF,DarzynkiewiczZ,Jhanwar-UniyalM,DaiW.CellcyclearrestandapoptosisinducedbyhumanPolo-likekinase3ismediatedthroughperturbationofmicrotubuleintegrity.MolCellBiol.2002May;22(10):3450-9.WeissRS,MatsuokaS,ElledgeSJ,LederP.Hus1actsupstreamofchk1inamammalianDNAdamageresponsepathway.CurrBiol.2002Jan8;12(1):73-7.XieS,WangQ,WuH,CogswellJ,LuL,Jhanwar-UniyalM,DaiW.Reactiveoxygenspecies-inducedphosphorylationofp53onserine20ismediatedinpartbypolo-likekinase-3.JBiolChem.2001Sep28;276(39):36194-9.XieS,WuH,WangQ,CogswellJP,HusainI,ConnC,StambrookP,Jhanwar-UniyalM,DaiW.Plk3functionallylinksDNAdamagetocellcyclearrestandapoptosisatleastinpartviathep53pathway.JBiolChem.2001Nov16;276(46):43305-12.YardenRI,Pardo-ReoyoS,SgagiasM,CowanKH,BrodyLC.BRCA1regulatestheG2/McheckpointbyactivatingChk1kinaseuponDNAdamage.NatGenet.2002Mar;30(3):285-9.ZhaoH,Piwnica-WormsH.ATR-mediatedcheckpointpathwaysregulatephosphorylationandactivationofhumanChk1.MolCellBiol.2001Jul;21(13):4129-39.
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