Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP 英文参考文献.docVIP

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Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP 英文参考文献.doc

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Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP 英文参考文献

Pax6RepressesAndrogenReceptor-Mediated TransactivationbyInhibitingRecruitmentofthe CoactivatorSPBP JulianneElvenes.,ErnstIvanSimonThomassen.,SylviaSagenJohnsen,KatrineKaino,EvaSj?ttem*, TerjeJohansen MolecularCancerResearchGroup,InstituteofMedicalBiology,UniversityofTroms?,Troms?,Norway Abstract Theandrogenreceptor(AR)hasacentralroleindevelopmentandmaintenanceofthemalereproductivesystemandinthe etiologyofprostatecancer.ThetranscriptionfactorPax6hasrecentlybeenreportedtoactasarepressorofARandtobe hypermethylatedinprostatecancercells.SPBPisatranscriptionalregulatorthatpreviouslyhasbeenshowntoenhancethe activityofPax6.InthisstudywehaveidentifiedSPBPtoactasatranscriptionalcoactivatorofAR.WealsoshowthatPax6 inhibitsSPBP-mediatedenhancementofARactivityontheARtargetgeneprobasinpromoter,arepressionthatwaspartly reversedbyincreasedexpressionofSPBP.EnhancedexpressionofPax6reducedtheamountofSPBPassociatedwiththe probasinpromoterwhenassayedbyChIPinHeLacells.WemappedtheinteractionbetweenbothARandSPBP,andARand Pax6totheDNA-bindingdomainsoftheinvolvedproteins.FurtherbindingstudiesrevealedthatPax6andSPBPcompete for binding to AR. These results suggest that Pax6 represses AR activity by displacing and/or inhibiting recruitment of coactivators to AR target promoters. Understanding the mechanism for inhibition of AR coactivators can give rise to moleculartargeteddrugsfortreatmentofprostatecancer. Citation: Elvenes J, Thomassen EIS, Johnsen SS, Kaino K, Sj?ttem E, et al. (2011) Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting RecruitmentoftheCoactivatorSPBP.PLoSONE6(9):e24659.doi:10.1371/journal.pone.0024659 Editor:Dong-YanJin,UniversityofHongKong,HongKong ReceivedMarch22,2011;AcceptedAugust16,2011;PublishedSeptember15,2011 Copyright: ? 2011 Elvenes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsource