Cell Cycle Regulation by the PRMT6 Arginine Methyltransferase through Repression of Cyclin-Dependent Kinase Inhibitors 英文参考文献.docVIP

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Cell Cycle Regulation by the PRMT6 Arginine Methyltransferase through Repression of Cyclin-Dependent Kinase Inhibitors 英文参考文献.doc

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Cell Cycle Regulation by the PRMT6 Arginine Methyltransferase through Repression of Cyclin-Dependent Kinase Inhibitors 英文参考文献

CellCycleRegulationbythePRMT6Arginine MethyltransferasethroughRepressionofCyclin- DependentKinaseInhibitors MarkusA.Kleinschmidt,PetradeGraaf,HettyA.A.M.vanTeeffelen,H.Th.MarcTimmers* DepartmentofMolecularCancerResearchandNetherlandsProteomicsCenter,UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands Abstract PRMT6 belongs to the family of Protein Arginine Methyltransferase (PRMT) enzymes that catalyze the methylation of guanidinonitrogensofarginineresidues.PRMT6hasbeenshowntomodifythetailofhistoneH3,buttheinvivofunctionof PRMT6islargelyunknown.Here,weshowthatPRMT6regulatescellcycleprogression.KnockdownofPRMT6expressionin thehumanosteosarcomacelllineU2OSresultsinanaccumulationofcellsattheG2checkpoint.LossofPRMT6coincides withupregulationofp21andp27,twomembersoftheCIP/KIPfamilyofcyclin-dependentkinase(CDK)inhibitors.Gene expression and promoter analysis show that p21 and p27 are direct targets of PRMT6, which involves methylation of arginine-2ofhistoneH3.OurfindingsimplyargininemethylationofhistonesbyPRMT6incellcycleregulation. Citation: Kleinschmidt MA, de Graaf P, van Teeffelen HAAM, Timmers HTM (2012) Cell Cycle Regulation by the PRMT6 Arginine Methyltransferase through RepressionofCyclin-DependentKinaseInhibitors.PLoSONE7(8):e41446.doi:10.1371/journal.pone.0041446 Editor:AxelImhof,Ludwig-Maximilians-Universita¨t Mu¨nchen,Germany ReceivedOctober4,2010;AcceptedJune27,2012;PublishedAugust20,2012 Copyright:?2012Kleinschmidtetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwasfinanciallysupportedbygrantsfromNWO-TOP(#700.57.302)andNetherlandsProteomicsCentertoHTMT.Thefundershadnorolein studydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:h.t.m.timmers@umcutrecht.nl Introduction ce