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1、THEJOURNALOFBIOLOGICALCHEMISTRYVOL.287,NO.12,pp.8662–8674,March16,2012©2012byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.PublishedintheU.S.A.Ligand-dependentCorepressor(LCoR)RecruitmentbyKrüppel-likeFactor6(KLF6)RegulatesExpressionoftheCyclin-dependentKinaseInhibitorCDKN1AGene*□SRecei
2、vedforpublication,October7,2011,andinrevisedform,January23,2012Published,JBCPapersinPress,January25,2012,DOI10.1074/jbc.M111.311605‡1‡‡§¶MarioR.Calderon,MarkVerway,Beum-SooAn,AnalisaDiFeo,TarekA.Bismar,DavidK.Ann,§‡‡‡2JohnA.Martignetti,TaliShalom-Barak**,andJohnH.White‡‡‡§FromtheDepartmentsofPhys
3、iologyandMedicine,McGillUniversity,Montreal,QuebecH3G1Y6,Canada,theDepartmentsofGeneticsandGenomicsSciencesandOncologicalSciences,MountSinaiSchoolofMedicine,NewYork,NewYork10029,the¶DepartmentofPathologyandLaboratoryMedicine,UniversityofCalgary,Calgary,AlbertaT2V1P9,Canada,theDepartmentofMolecula
4、rPharmacology,CityofHopeBeckmanResearchInstitute,Duarte,California91010,andthe**DepartmentofOBGYNandReproductiveSciences,Magee-Women’sResearchInstitute,UniversityofPittsburgh,Pittsburgh,Pennsylvania15213Background:Ligand-dependentcorepressor(LCoR)wasidentifiedasarepressorofnuclearhormonereceptors.
5、Results:AscreenfornewinteractingfactorsrevealedthatLCoRactswithKrüppel-likefactor6(KLF6)torepressCDKN1Agenetranscription.Conclusion:KLF6inhibitsgenetranscriptionbytetheringacomplexofproteinsincludingLCoRtoDNA.DownloadedfromSignificance:IdentificationofanovelmechanismofactionofLCoR,independentofnuc
6、learreceptors,withpotentialimpli-cationsforprostatecancer.Thewidelyexpressedtranscriptionalcoregulator,ligand-de-CDKN1Ageneandothergenesaswellbytetheringatranscrip-pendentcorepressor(LCoR),initiallycharacterizedasaregula-tionalcorepressorcomplexcontainingLCoR,withspecificcon-http://www.jbc.org/tor
7、ofnuclearreceptor-mediatedtransactivation,functionstributionsbyCtBP1andHDACs.throughrecruitmentofC-terminalbindingproteins(CtBPs)andhistonedeacetylases(HDACs)toitsN-terminalandcentraldomains,respectively.Weperfor
