CARM1 and Regulation of the Estrogen Receptor

Severalformsofpost-translationalmodificationregulateproteinactivities.Recently,proteinmethylationbyCARM1(coactivator-associatedargininemethyltransferase1)hasbeenobservedtoplayakeyroleintranscriptionalregulation.CARM1associateswiththep160classoftranscriptionalcoactivatorsinvolvedingeneactivationbysteroidhormonefamilyreceptors.CARM1alsointeractswithCBP/p300transcriptionalcoactivatorsinvolvedingeneactivationbyalargevarietyoftranscriptionfactors,includingsteroidhormonereceptorsandCEBP.OnetargetofCARM1isthecorehistonesH3andH4,whicharealsotargetsofthehistoneacetylaseactivityofCBP/p300coactivators.RecruitmentofCARM1tothepromoterregionbybindingtocoactivatorsincreaseshistonemethylationandmakespromoterregionsmoreaccessIBLefortranscription.AnothertargetofCARM1methylationisacoactivatoritinteractswith,CBP.MethylationofCBPbyCARM1blocksCBPfromactingasacoactivatorforCREBandredirectsthelimitedCBPpoolinthecelltobeavailableforsteroidhormonereceptors.Otherformsofpost-translationalproteinmodificationsuchasphosphorylationarereversibleinnature,butasofyetaproteindemethylaseisnotknown.ThemethylationactivityofCARM1modulatestheactivityofspecifictranscriptionalregulators.CARM1actsasacoactivatorforthemyogenictranscriptionfactorMef2c,andisnecessaryfornormalmusclecelldifferentiation.TheestrogenreceptorisanothertranscriptionfactorthatusesCARM1asoneofseveralcoactivators,actingsynergisticallywithCBPthroughtheGrip1memberofthep160familyofcoactivators.Theinteractionofestrogenreceptorwithvariousligand-dependentcoactivatorsmayproducethetissueselectiveresponseofsomeestrogenreceptorligandsliketamoxifen.

Contributor:KosiGramatikoff,PhD

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