Proline-,glutamicacid-,leucine-richprotein1(Pelp1alsoknownas:modulatorofnongenomicactivityofestrogenorMNAR)isarecentlydiscoveredtransmitterofestrogensignals.Thereceptorsforestrogen(ER),progestin(PR),androgen(AR)andothersaresteroidhormonereceptors,whicharepartofalargefamilyofligand-inducIBLetranscriptionfactors.Ithasbeenestablishedthatestrogenhasatleasttwocoursesofactiontermedclassicalorgenomicandnongenomic.TheclassicalactivationcascadeiswellknownandanexampleofthisisillustratedintheCarm1pathway.ThenongenomicornontranscriptionalactivationcascadefortheestrogenreceptorwasdeterminedbasedontherapidresponsetimesobservedfortheactivationoftheMAPKcascadeandothercellproliferationeffects.ThemechanismwasbelievedtoinvolveamembraneboundERbutattemptstoisolatesuchaproteinhavenotbeensuccessful.AsecondpossibilitywouldinvolveascaffoldproteinthatinteractswithER.Pelp1appearstofitthesecondscenario.Pelp1wasfirstisolatedbyVadlamudietalasacoactivatoroftranscriptionforER-alpha.TheyobservedthatPelp1wasexpressedatlevels3–5timesnormalinbreasttumors.SeveralbreastcancercelllineshavebeenshowntoexpressPelp1.VadlamudietalalsoshowedthatlikemanynuclearhormonereceptorsPelp1alsointeractswithCbpandp300.MorerecentlyWongetal.demonstratedthatPelp1mediatestheinteractionofERandSrcleADIngtotheactivationoftheMitogenAactivatedProteinKinasesErk1andErk2.

Contributor:RogerAndersonPh.D.

REFERENCES:VadlamudiRK,WangRA,MazumdarA,KimY,ShinJ,SahinA,KumarR.MolecularcloningandcharacterizationofPELP1,anovelhumancoregulatorofestrogenreceptoralpha.JBiolChem.2001Oct12;276(41):38272-9.WongCW,McNallyC,NickbargE,KommBS,CheskisBJ.Estrogenreceptor-interactingproteinthatmodulatesitsnongenomicactivity-crosstalkwithSrc/Erkphosphorylationcascade.ProcNatlAcadSciUSA.2002Nov12;99(23):14783-8.