Seeonlineversionforlegendandreferences.848Cell143,November24,2010©2010ElsevierInc.DOI10.1016/j.cell.2010.11.026SnapShot:TheSUMOSystemSandrineCretonandStefanJentschMaxPlanckInstituteofBiochemistry,Martinsried82152,GermanyKSnapShot:TheSUMOSystemSandrineCretonandStefanJentschMaxPlanckInstituteofBiochemistry,Martinsried82152,Germany848.e1Cell143,November24,2010©2010ElsevierInc.DOI10.1016/j.cell.2010.11.026SUMO(smallubiquitin-relatedmodifier)isahighlyconservedeukaryoticmemberofthefamilyofubiquitin-relatedproteins.Despitelimitedsequencesimilarity,SUMOandubiquitinhavehighlyhomologousstructures(i.e.,witharoot-mean-squaredeviation[rmsd]differenceof2.1Å).Likeubiquitin,SUMOiscovalentlyattachedtootherproteins(SUMOylation)andthusfunctionsasaposttranslationalmodifier.Althoughamajorfunctionofubiquitinationistopromoteproteindegradation,SUMOylationdoesnotusuallytriggerproteolyisoftheconjugatedprotein.Instead,amainfunctionofSUMOylationistofoster—andoccasionallydisrupt—protein-proteininteractions.Althoughlessfrequentthanubiquitination,SUMOylationregulatesnumerousprocessesandhasmanysubstratesinthecytosolandthenucleus.LowereukaryotespossessonlyoneSUMOform,buthighereukaryotesexpressseveral,perhapsfunctionallydistinct,SUMOvariants.Inmostorganisms,SUMOisessentialforviability.ThisSnapShotdepictsthereactionsinvolvedinSUMOligation,theeffectsofSUMOylationontargetproteins,andcellularprocessesregulatedbySUMOylation.SUMOEnzymologySimilartoubiquitination,SUMOylationrequiresATPandaseriesofenzymesforconjugation(TableA).SUMOisinitiallyproducedasaninactiveprecursor,whichisthenpro-cessedattheCterminusbySUMO-specificproteases(yeastUlp1,mammalianSENPs),givingrisetomatureSUMOwithaC-terminalGly-Glymotif.Conjugationinvolvesatleasttwoenzymes,anATP-dependentactivatingenzyme(E1,aheterodimer)andaconjugatingenzyme(E2,Ubc9).SUMOislinkedtotheseenzymesbytheformationofathioesterbondbetweenSUMO’sCterminusandcysteineresiduesintheactivesitesoftheseenzymes.Forsomesubstrates,SUMOylationfurtherrequiresspecificSUM...