GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling 英文参考文献.docVIP

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GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling 英文参考文献.doc

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GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling 英文参考文献

GPR50InteractswithTIP60toModulateGlucocorticoid ReceptorSignalling JianLi,LauraE.Hand,Qing-JunMeng,AndrewS.I.Loudon*,DavidA.Bechtold* FacultyofLifeSciences,UniversityofManchester,Manchester,UnitedKingdom Abstract GPR50isanorphanG-proteincoupledreceptormostcloselyrelatedtothemelatoninreceptors.Thephysiologicalfunction ofGPR50remainsunclear,althoughourpreviousstudiesimplicatethereceptorinenergyhomeostasis.Here,wereveala roleforGPR50asasignallingpartnerandmodulatorofthetranscriptionalco-activatorTIP60.Thisinteractionwasidentified inayeast-two-hybridscreen,andconfirmedbyco-immunoprecipitationandco-localisationofTIP60andGPR50inHEK293 cells.Co-expressionwithTIP60increasedperinuclearlocalisationoffulllengthGPR50,andresultedinnucleartranslocation ofthecytoplasmictailofthereceptor,suggestingafunctionalinteractionofthetwoproteins.Wefurtherdemonstratethat GPR50canenhanceTIP60-coactiavtionofglucocorticoidreceptor(GR)signalling.Inlinewithinvitroresults,repressionof pituitaryPomcexpression,andinductionofgluconeogenicgenesinliverinresponsetotheGRagonist,dexamethasone wasattenuatedinGpr502/2mice.TheseresultsidentifyanovelroleforGPR50inglucocorticoidreceptorsignallingthrough interactionwithTIP60. Citation:LiJ,HandLE,MengQ-J,LoudonASI,BechtoldDA(2011)GPR50InteractswithTIP60toModulateGlucocorticoidReceptorSignalling.PLoSONE6(8): e23725.doi:10.1371/journal.pone.0023725 Editor:VincentLaudet,EcoleNormaleSupe′rieuredeLyon,France ReceivedFebruary2,2011;AcceptedJuly26,2011;PublishedAugust17,2011 Copyright:?2011Lietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was funded by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC #BBE0104901, www.bbsrc.ac.uk/). The fundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theaut