Roles of the Kinase TAK1 in TRAF6-Dependent Signaling by CD40 and Its Oncogenic Viral Mimic, LMP1 英文参考文献.docVIP

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Roles of the Kinase TAK1 in TRAF6-Dependent Signaling by CD40 and Its Oncogenic Viral Mimic, LMP1 英文参考文献.doc

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Roles of the Kinase TAK1 in TRAF6-Dependent Signaling by CD40 and Its Oncogenic Viral Mimic, LMP1 英文参考文献

RolesoftheKinaseTAK1inTRAF6-DependentSignaling byCD40andItsOncogenicViralMimic,LMP1 KellyM.Arcipowski1,GailA.Bishop2,3* 1InterdisciplinaryGraduatePrograminMolecularandCellularBiology,UniversityofIowa,IowaCity,Iowa,UnitedStatesofAmerica,2InterdisciplinaryGraduateProgram inMolecularandCellularBiology,DepartmentsofMicrobiologyandInternalMedicine,UniversityofIowa,IowaCity,Iowa,UnitedStatesofAmerica,3VeteransAffairs MedicalCenter,IowaCity,Iowa,UnitedStatesofAmerica Abstract The Epstein-Barr virus (EBV)-encoded protein latent membrane protein 1 (LMP1) is essential for EBV-mediated B cell transformationandplaysacriticalroleinthedevelopmentofpost-transplantBcelllymphomas.LMP1alsocontributesto theexacerbationofautoimmunediseasessuchassystemiclupuserythematosus(SLE).LMP1isafunctionalmimicofthe tumor necrosis factor receptor (TNFR) superfamily member CD40, and relies on TNFR-associated factor (TRAF) adaptor proteinstomediatesignaling.However,LMP1activationsignalstotheBcellareamplifiedandsustainedcomparedtoCD40 signals.WepreviouslydemonstratedthatLMP1andCD40useTRAFmoleculesdifferently.AlthoughassociatingwithCD40 andLMP1viaseparatemechanisms,TRAF6playsasignificantroleinsignaltransductionbyboth.Itisunknownwhether TRAF6mediatesCD40versusLMP1functionsviadistinctorsharedpathways.Inthisstudy,wetestedthehypothesisthat TRAF6 uses the kinase TAK1 to trigger important signaling pathways following both CD40 and LMP1 stimulation. We determinedthatTAK1wasrequiredforJNKactivationandinterleukin-6(IL-6)productionmediatedbyCD40andLMP1,in both mouse and human B cells. Additionally, TRAF3 negatively regulated TRAF6-dependent, CD40-mediated TAK1 activationbylimitingTRAF6recruitment.ThismodeofregulationwasnotobservedforLMP1andmaycontributetothe dysregulationofLMP1comparedtoCD40signals. Citation:ArcipowskiKM,BishopGA(2012)RolesoftheKinaseTAK1inTRAF6-DependentSignalingbyCD40andItsOncogenicViralMimic,LMP1.PLoSONE7(7): e42478.doi:10.1371/journal.pone.0042478 Editor:EstherLutgens,UniversityofAmsterdam