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,2006,3(3):2122215JMedMolBiol,2006,3(3):2122215:(No10471589):,,1976,:(:010265296474,E2mail:heweiimu@public1bta1net1cn)ThisworkwassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina(No10471589)Authorsbriefintroduction:LIUShirong1Male,bornin1976,GraduatestudentformasterdegreeCorrespondingauthor:HEWei(Tel:86210265296474,E2mail:he2weiimu@public1bta1net1cn)SUMO:,100005SUMO,SUMO,SUMO,SUMOSUMODNA,SUMO;Q7Sumoylation2AMultifunctionalPost2translationalProteinModificationLIUShirong,HEWeiDepartmentofImmunology,InstituteofBasicMedicalSciences&SchoolofBasicMedicine,ChineseAcademyofMedicalSciences&PekingUnionMedicalCollege,Beijing,100005,ChinaAbstractThesmallubiquitin2relatedmodifier(SUMO)familyproteinsarestructurallyandmechanisticallyrelatedtoubiquitin1Otherthandegradationofubiquitinizedtargetproteinsbythe26Sproteasome,sumoylationappearstoplayimportantrolesinproteintargetingandfunctionalregu2lationofsubstrateproteins1Recentresearchrevealedthatsumoylationisinvolvedinmitochondrialfission,DNArepair,theionchannelcontrolandcircadianclock1Manydiseasesordisordersareshowntoberelatedtosumoylation/desumoylationcycle1Keywordssmallubiquitin2relatedmodifierproteins;proteinprocessing,post2translational,,,,26S(smallubiquitin2relatedmodifier,SUMO),,,,1SUMOSUMOSUMO111SUMOSUMO,4SUMO,SUMO21SUMO22SUMO23SUMO24SUMO22SUMO23,SUMO22/3SUMO21,SUMO22/3SUMO244SU2MO[1],SUMO24TAB2,SU2MO22,SUMO23SUMO24,SUMO21,SUMO22/3©1994-2008ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[2]SUMO,SUMO,:2Lys2X2Glu(,L,IV,X)[3]SUMO21,V/I2X2V/I2V/I,SU2MO,SUMO(SUMO2123),SUMO[4]112SUMOSUMOSUMO(1)[2]SUMOC,Ulp1CSUMOSUMO(E1)(Uba2Aos1)ATP2SUMO2,Uba2SUMOSUMO(E2)Ubc9,Ubc9SUMOSUMOSUMO(E3),SUMOSUMOUlp1Ulp2,SUMOSUMO1SUMO11211SUMO(E1),SUMO,SUMOSUMO(E1)Aos1(SAE1,Sua1)Uba2(SAE2),NCATP,SUMO,SUMOUba2[2,5]11212SUMO(E2),SUMOSUMOUba2SUMO(E2),Ubc9,SUMO2Ubc9Ubc9,(nuclearporecomplex,NPC),NPC[6]11213SUMO(E3),E1,E2SUMO,,SUMO(E3)3SU2MO(PIAS,RanBP2PC2)Ubc9,SUMO11214SUMO,SU2MO,C,,SUMO,SUMO(SUMO),SUMOq,,Ulp1Ulp2/Smt4,Ulp1,Ulp1;Ulp2Ulp1SUMOC,Ulp2SUMO[7]7,SENP127,,,SENPSUMO[3]2SUMOSUMO,,SUMO;,SUMO,SUMO,(1)SUMO,,,312,2006,3(3):2122215JMedMolBiol,2006,3(3):2122215©1994-2008ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[3,8],SU2MO,,1SUMOSUMO[2,6,9212]SUMO()SUMOPCNA,DNARanGAPNPC,RanBP2IBNEMO/IKKPMLPML,PML/ND10SP100,Daxx,ND10SMAD4,SMAD4HIPK2,HIPK3P63P63,P53GATA4GATA4,SUMOGATA4SP3,SP3H4Elk21HDAC,Elk21P300SUMOP300HDAC6,P300(PR)SUMO21PR(AR)ARSTAT1IFNHSF2DNACREB,CREB,211SUMODynaminDRP1(mammalianorthologueofS1cerevisiaeDnm1),Ubc9SUMO,,DRP1SUMODRP12SUMO,,SUMO21DRP1,,SUMO[13]212SUMODNA(proliferatingcellnuclearanti2gen,PCNApol30)S,SUMO[14]SU2MOSrs2p,Srs2pSrs2pSUMOPCNA,Srs2p[15216]213SUMO22P(two2PloopK+leak,K2P)K2P1mRNA,K2P1K2P1K+pHSUMO[17]SUMO,K2P1,K2P1274K2P1SUMO,SU2MOK2P1SUMOSUMOSUMOSUMO[18]214SUMOCLOCKBMAL1(brainandmusclearylhy2drocarbonreceptornucleartransporterlikeprotein21,21),DNAE2box,Cardone[19],BMAL1SUMO,K259SUMO,BMAL1SUMOCLOCKBmal1-/-(Bmal1)E2box(Dbp),BMAL1412,.SUMO:©1994-2008ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(K259R),Dbp,SUMO215SUMOSUMOSUMO(A),SUMO23,SUMOA,SUMO232K11R(SUMO),SUMOA,SUMOA[20](polyQ)(HD)Machado2Joseph,SUMO21,SUMOpolyQHDHuntingtin(Htt)polyQ,SUMO,,SUMOSUMOHtt,,SUMOHtt,[21],SUMO24,55MetVal(SUMO24MSUMO24V),SUMO24M1,HSF1/HSF2SUMO24(M)[1]31996SUMO,SUMO,,SUMO?SUMO,,SUMO,,SUMO,SUMO[1]BOHRENKM,NADKARNIV,SONGJH,etal1AM55Vpol2ymorphisminanovelSUMOgene(SUMO24)differentiallyacti2vatesheatshocktranscriptionfactorsandisassociatedwithsuscep2tibilitytotypeIdiabetesmellitus[J]1JBiolChem,2004,279(26):272332272381[2]DOHMENRJ.SUMOproteinmodification[J]1SUMOproteinmo2dification[J]1BiochimBiophysActa,2004,1695(1-3):11321311[3],1-SUMO[J]1,2004,26(1):10214[4]SONGJ,DURRINLK,WILKINSONTA,etal1IdentificationofaSUMO2bindingmotifthatrecognizesSUMO2modifiedproteins[J]1ProcNatlAcadSciUSA,2004,101(40):143732143781[5]JOHNSONES1ProteinmodificationbySUMO[J]1AnnuRevBiochem,2004,73:35523821[6]GRESKOE,MOLLERA,ROSCICA,etal1Covalentmodifica2tionofhumanhomeodomaininteractingproteinkinase2bySUMO21atlysine25affectsitsstability[J]1BiochemBiophysResCom2mun,2005,329(4):1293212991[7]SCHWIENHORSTI,JOHNSONES,DOHMENRJ1SUMOcon2jugationanddeconjugation[J]1MolGenGenet,2000,263(5):77127861[8],1SUMO[J]1,2004,16(1):126[9]WANGJ,FENGXH,SCHWARTZRJ1SUMO21modificationactivatedGATA42dependentcardiogenicgeneactivity[J]1JBiolChem,2004,279(47):490912490981[10]PICHLERA,GASTA,SEELERJS,etal1Melchior1Thenucle2oporinRanBP2hasSUMO1E3ligaseactivity[J]1Cell,2002,108(1):10921201[11]PICHLERA,KNIPSCHEERP,SAITOHH,etal1TheRanBP2SUMOE3ligaseisneitherHECT2norRING2type[J]1NatStructMolBiol,2004,11(10):98429911[12]GHIONIP,D’ALESSANDRAY,MANSUETOG,etal1Thepro2teinstabilityandtranscriptionalactivityofp63areregulatedbySUMO21conjugation[J]1CellCycle,2005,4(1):18321901[13]HARDERZ,ZUNINOR,MCBRIDEH1Sumo1conjugatesmito2chondrialsubstratesandparticipatesinmitochondrialfission[J]1CurrBiol,2004,14(4):34023451[14]HOE