REVIEWnpgCellResearch(2016)26:457-483.www.nature.com/crUbiquitinsignalinginimmuneresponsesHongboHu1,Shao-CongSun2,31DepartmentofRheumatologyandImmunology,StateKeyLaboratoryofBiotherapy&CollaborativeInnovationCenterforBio-therapy,WestChinaHospital,SichuanUniversity,Chengdu610041,China;2DepartmentofImmunology,TheUniversityofTexasMDAndersonCancerCenter,7455FanninStreet,Unit902,Houston,TX77030,USA;3TheUniversityofTexasGraduateSchoolofBiomedicalSciences,Houston,TX77030,USAUbiquitinationhasemergedasacrucialmechanismthatregulatessignaltransductionindiversebiologicalpro-cesses,includingdifferentaspectsofimmunefunctions.Ubiquitinationregulatespattern-recognitionreceptorsig-nalingthatmediatesbothinnateimmuneresponsesanddendriticcellmaturationrequiredforinitiationofadaptiveimmuneresponses.Ubiquitinationalsoregulatesthedevelopment,activation,anddifferentiationofTcells,therebymaintainingefficientadaptiveimmuneresponsestopathogensandimmunologicaltolerancetoself-tissues.Likephosphorylation,ubiquitinationisareversiblereactiontightlycontrolledbytheopposingactionsofubiquitinligasesanddeubiquitinases.Deregulatedubiquitinationeventsareassociatedwithimmunologicaldisorders,includingauto-immuneandinflammatorydiseases.Keywords:ubiquitination;innateimmunity;adaptiveimmunity;Tcellactivation;immunetolerance;autoimmunity;NF-κB;Peli1;TRAFCellResearch(2016)26:457-483.doi:10.1038/cr.2016.40;publishedonline25March2016Correspondence:Shao-CongSunTel:+1-713-563-3218Email:ssun@mdanderson.orgIntroductionUbiquitinationisaposttranslationalmechanismofproteinmodificationinvolvingcovalentconjugationofubiquitintolysine(K)residuesoftargetproteins,aprocessthatiscatalyzedbythesequentialactionofubiquitin-activating(E1),ubiquitin-conjugating(E2),andubiquitin-ligating(E3)enzymes[1].Formationofpolyubiquitinchainsinvolvesisopeptidebondconnec-tionbetweenthecarboxyl-terminalglycineresidueofubiquitinandaninternalKresidueortheamino-terminalmethionine(M1)ofanotherubiquitin.ThepresenceofsevenKs,alongwiththeM1,createsa...
