Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway 英文参考文献.docVIP

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Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway 英文参考文献.doc

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Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway 英文参考文献

Rasd1ModulatestheCoactivatorFunctionofNonOin theCyclicAMPPathway ShufenAngelineOng1,JenJenTan1,2,WaiLoonTew1,Ken-ShiungChen1* 1SchoolofBiologicalSciences,DepartmentofGenomicsandGenetics,NanyangTechnologicalUniversity,Singapore,Singapore,2AgencyforScience,Technologyand Research,Singapore,Singapore Abstract Alllivingorganismsexhibitautonomousdailyphysiologicalandbehaviouralrhythmstohelpthemsynchronizewiththe environment. Entrainment of circadian rhythm is achieved via activation of cyclic AMP (cAMP) and mitogen-activated proteinkinasesignalingpathways.NonO(p54nrb)isamultifunctionalproteininvolvedintranscriptionalactivationofthe cAMPpathwayandisinvolvedincircadianrhythmcontrol.Rasd1isamonomericGproteinimplicatedtoplayapivotalrole inpotentiatingbothphoticandnonphoticresponsesofthecircadianrhythm.Inthisstudy,wehaveidentifiedandvalidated NonOasaninteractingpartnerofRasd1viaaffinitypulldown,co-immunoprecipitationandindirectimmunofluorescence studies.TheGTP-hydrolysisactivityofRasd1isrequiredforthefunctionalinteraction.FunctionalinteractionofRasd1-NonO inthecAMPpathwaywasinvestigatedviareportergeneassays,chromatinimmunoprecipitationandgeneknockdown.We showedthatRasd1andNonOinteractattheCRE-siteofspecifictargetgenes.Thesefindingsrevealanovelmechanismby whichthecoregulatoractivityofNonOcanbemodulated. Citation: Ong SA, Tan JJ, Tew WL, Chen K-S (2011) Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway. PLoS ONE 6(9): e24401. doi:10.1371/journal.pone.0024401 Editor:JanetF.Partridge,St.JudeChildren’sResearchHospital,UnitedStatesofAmerica ReceivedJune14,2011;AcceptedAugust8,2011;PublishedSeptember7,2011 Copyright:?2011Ongetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyagrantfromtheSingaporeMinistryofEducation,AcademicResearchFundTier2(ARC3/04,awardedtoKen-