Negative Regulation of CEBPbeta1 by Sumoylation in Breast Cancer Cells 英文参考文献.docVIP

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Negative Regulation of CEBPbeta1 by Sumoylation in Breast Cancer Cells 英文参考文献.doc

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Negative Regulation of CEBPbeta1 by Sumoylation in Breast Cancer Cells 英文参考文献

NegativeRegulationofC/EBPbeta1bySumoylationin BreastCancerCells AllisonA.Atwood1,RachelJerrell2,LindaSealy1,2* 1DepartmentofCancerBiology,VanderbiltUniversitySchoolofMedicine,Nashville,Tennessee,UnitedStatesofAmerica,2DepartmentofMolecularPhysiologyand Biophysics,VanderbiltUniversitySchoolofMedicine,Nashville,Tennessee,UnitedStatesofAmerica Abstract Sumoylation is a post-translational modification that is oftentimes deregulated in diseases such as cancer. Transcription factors are frequent targets of sumoylation and modification by SUMO can affect subcellular localization, transcriptional activity,andstabilityofthetargetprotein.C/EBPbeta1isonesuchtranscriptionfactorthatismodifiedbySUMO-2/3.Non- sumoylatedC/EBPbeta1,p52-C/EBPbeta1,isexpressedinnormalmammaryepithelialcellsbutnotbreastcancercelllines and plays a role in oncogene-induced senescence, a tumor suppressive mechanism. Although p52-C/EBPbeta1 is not observedviaimmunoblotinbreastcancercelllines,highermolecularweightbandsareobservedwhenbreastcancercell linesaresubjectedtoimmunoblotanalysiswithaC/EBPbeta1-specificantibody.WeshowthatexogenouslyexpressedC/ EBPbeta1issumoylatedinbreastcancercells,andthatthehighermolecularweightbandsweobserveinanti-C/EBPbeta1 immunoblotsofbreastcancercelllinesissumoylatedC/EBPbeta1.Phosphorylationoftentimesenhancessumoylation,and phosphorylationcascadesareactivatedinbreastcancercells.WedemonstratethatphosphorylationofC/EBPbeta1Thr235 byErk-2enhancessumoylationofC/EBPbeta1invitro.Inaddition,sumoylatedC/EBPbeta1isphosphorylatedonThr235and mutationofThr235toalanineleadstoadecreaseinsumoylationofC/EBPbeta1.Finally,usingaC/EBPbeta1-SUMOfusion proteinweshowthatconstitutivesumoylationofC/EBPbeta1completelyblocksitscapabilitytoinducesenescenceinWI38 fibroblastsexpressinghTERT.Thus,sumolylationofC/EBPbeta1inbreastcancercellsmaybeamechanismtocircumvent oncogene-inducedsenescence. Citation:AtwoodAA,JerrellR,SealyL(2011)NegativeRegulationofC/EBPbeta1bySumoylationinBreastCancerCells.PLoSONE6(9