蛋白质SUMO化修饰研究进展-韦玮

ChinaBiotechnology,2008,28(7):122~126SUMO*韦玮1,2张浩1毛建平2叶棋浓1**(11008502100850)SUMO(smallubiquitin-relatedmodifier)是类泛素蛋白家族的重要成员之一,可与多种蛋白结合发挥相应的功能,其分子结构及SUMO化反应途径都与泛素类似,但二者功能完全不同SUMO化修饰可参与转录调节核转运维持基因组完整性及信号转导等多种细胞内活动,是一种重要的多功能的蛋白质翻译后修饰方式SUMO化修饰功能的失调可能导致某些疾病的发生SUMOSUMO化蛋白修饰UBC9PIASQ51:2008-04-10:2008-05-19*(30670439)(06J021)**,:[e-mail],,(ubiquitylation),76(ubiquitin,Ub),,,(ubiquitin-likeproteins,Ubls),,,,SUMO(smallubiquitin-relatedmodifier)SUMOs,SMT31995,[1],SUMO(sumoylation)SUMO(androgenreceptor,AR)IJBAc-jun(histonedeacetylases,HDACs)p53,DNA1SUMOSUMOs11kDa,18,NMR,,)B-(B-sheet)A-A-helix),CGlySUMON10~25,;,[2]SUMO,,SUMO,SUMOSUMO,:SUMO1(PIC1,UBL1,sentrin,GMP1SMT3C)SUMO2(SMT3Asentrin-3)SUMO3(SMT3Bsentrin-2)SUMO4SUMO1~SUMO3,SUMO4[3]2SUMO,SUMO,RanGAP1,PML,Sp100,IJBA,p53c-JunSUMO,7KXE,7,;KDOI10.13523/j.cb.200807252008,28(7):SUMO;X;ESUMOSUMO,(proliferatingcellnuclearantigen,PCNA)SUMOTKET;SUMO,Mdm2DaxxCREBCTBP-27KXE[4]3SUMO3.1SUMOSUMO,SUMO,C2~11SUMO(Ulp)C,CGly-Gly[5],SUMO3.2SUMO,SUMOCGlyLysE-,:E1,E2E3,E1,SAE1/SAE2,Aos1/Uba2,,[2]E2UBC9,E2;,E2,UBC9SUMOE2E3:PIASRanBP2/Nup358Pc2(polycombgroupprotein)[4]SUMO:(1):SUMOATPC;E1Uba2,AMP,E1SUMOC,SUMO;SUMOE2(2):SUMOE2UBC9,CUBC9SUMO-E2(3):UBC9SUMO,SUMOC,SUMO,E1E2SUMO[2]SUMOE3,E3SUMO,E2(UBC9),SUMOE23.3SUMOSUMO,SUMOUlp,,SUMOC(),SUMO;SUMOSUMO,SUMOSUMOUlp1Ulp2,Ulp1(nuclearporecomplex,NPC),CSUMO;Ulp2/Smt4,C,SUMOSUMO,SENP,,[4]4SUMOSUMO120,,SUMO,4.1,SUMO,SUMOElk-1,Sp-3,SREBPs,STAT-1,SRF,c-myb,C/EBPs,p300(androgenreceptor,AR)(progesteronereceptor,PR),SUMO,SUMODNA,HDAC6,Daxx,CHD3/ZFHPIAS,,SUMOHSF1,HSF2B-cateninTcf-4123ChinaBiotechnologyVo.l28No.72008[4],SUMO,4.2PMLNBsPML(PMLnuclearbodies,PMLNBs)SUMO,,[6],PMLPMLNBsPMLSUMONBs,NBSp100Daxx,HDAC1,CBP,p53,Sp3LEF1p53,LEF1,Sp100,Daxx,SRFIE1IE2NBSUMO,P53CBPPMLNBs[4],SUMONB,NBSUMO4.3,SUMOS.pombeSUMO,,DNA,S.cerevisiaeulp2v,rDNA[4],SUMOSUMO(SMT3)Mif2p/Cenp-C,Cenp-C,II(topoisomeraseII,top2)RanGAP1SUMO,Cenp-C;HeLaSUMORanGAP1;top2SUMO,SUMOSUMO[6]4.4DNADNA,SUMOE3Mms21/Nse2Smc5/6SUMODNA,E3DNA[7~10]PCNADNA,G2SSUMOPCNA(Lys164),,DNASUMO[4]4.5,SUMO,,,NF-JBIJBA,TNF,IJBA26S,NF-JB,SUMOIJBALys,-,SUMOIJBA,NF-JB[2]IJBA,Smad4[11],Huntingtin[12]SUMO4.6RanGAP1SUMOSUMORanGAP1,GTPRan(nuclearporecomplex,NPC),RanNPC,RanGAP1SUMONPC[6]SUMO,,SUMO,SUMOFAK,PTP1B[13];,NFkBIkBaGlut4SOD1[14]SUMO,FasTNFR1SUMO,4.7SUMO,SUMO,SUMO,,Gam11242008,28(7):SUMOSUMOE1Gam1RINGE1,SUMO[15~17],SUMO,5SUMO,SUMO,SUMO,,SUMO,SUMO2E1Uba2[18]UBC9E2[19]E3PIAS3[20]SUMOSENP1;SENP1[21]SUMO,[6],SUMOBohren[22]1(T1DM)SUMO4[3],M55VT1DM,SUMO()()SUMOSUMO,[6]6SUMO,,;SUMO,SUMO,SUMO,(),,[5],SUMO,SUMO,,E3SUMO,E3,SUMO,[6],[1]MeluhPB,KoshlandD.EvidencethattheMIF2geneofSaccharomycescerevisiaeencodesacentromereproteinCENP-C.MolBiolCel,l1995,6:793~807[2],.SUMO.,2004,16(1):1~6ChenQ,ShiYY.LifeScience.2004,16(1):1~6[3]GuoD,LiM,ZhangY,eta.lAfunctionalvariantofSUMO4,anewIkappaBalphamodifier,isassociatedwithtype1diabetes.NatGene,t2004,36:837~841[4]JohnsonES.ProteinmodificationbySUMO.AnnuRevBiochem,2004,73:355~382[5]Geiss-FriedlanderR,MelchiorF.Conceptsinsumoylation:adecadeon.NatRevMolCellBio,l2007,8(12):947~956[6]ZhaoJ.Sumoylationregulatesdiversebiologicalprocesses.CellMolLifeSc,i2007,64(23):3017~3033[7]AndrewsEA,PalecekJ,SergeantJ,eta.lNse2,acomponentoftheSmc56complex,isaSUMOligaserequiredfortheresponsetoDNAdamage.MolCellBio.,2005,25:185~196[8]McDonaldWH,PavlovaY,YatesJR,eta.lNovelessentialDNArepairproteinsNse1andNse2aresubunitsofthefissionyeastSmc5-Smc6complex.JBiolChem,2003,278:45460~45467[9]ZhaoX,BlobelG.ASUMOligaseispartofanuclearmultiproteincomplexthataffectsDNArepairandchromosomalorganization.ProcNatlAcadSciUSA,2005,102:4777~4782125ChinaBiotechnologyVo.l28No.72008[10]PottsPR,YuH.HumanMMS21/NSE2isaSUMOligaserequiredforDNArepair.MolCellBio,l2005,25:7021~7032[11]LinX,LiangM,LiangYY,eta.lSUMO-1/Ubc9promotesnuclearaccumulationandmetabolicstabilityoftumorsuppressorSmad4.JBiolChem,2003,278:31043~31048[12]SteffanJS,AgrawalN,PallosJ,eta.lSUMOmodificationofHuntingtinandHuntingtons'diseasepathology.Science,2004,304:100~104[13]DadkeS,CotteretS,YipSC,eta.lRegulationofproteintyrosinephosphatase1Bbysumoylation.NatCellBio,l2007,9:80~85[14]FeiE,JiaN,YanM,eta.lSUMO-1modificationincreaseshumanSOD1stabilityandaggregation.BiochemBiophysResCommun,2006,347:406~412[15]BoggioR,ColomboR,HayRT,eta.lAmechanismforinhibitingtheSUMOpathway.MolCel,l2004,16:549~561[16]BoggioR,ChioccaS.Gam1andtheSUMOpathway.CellCycle,2005,4:533~535[17]BoggioR,PassafaroA,ChioccaS.TargetingSUMOE1toubiquitinligases:aviralstrategytocounteractsumoylation.JBiolChem,2007,282:15376~15382[18]LeeJS,ThorgeirssonSS.Genome-scaleprofilingofgeneexpressioninhepatocellularcarcinoma:classification,survivalprediction,andidentificationoftherapeutictargets.Gastroenterology,2004,127:S51~S55[19]MoYY,YuY,TheodosiouE,eta.lAroleforUbc9intumorigenesis.Oncogene,2005,24:2677~2683[20]WangL,BanerjeeS.DifferentialPIAS3expressioninhumanmalignancy.OncolRep,2004,11:1319~1324[21]ChengJ,BawaT,LeeP,eta.lRoleofdesumoylationinthedevelopmentofprostatecancer.Neoplasia,2006,8:667~676[22]BohrenKM,NadkarniV,Son