泛素-蛋白酶体途径的生物学功能

:2005-09-07;:2005-10-07:(1975-),,,,::(30460006)24220064JIANGXISCIENCEVol.24No.2Apr.2006:1001-3679(2006)02-0155-05,(,330047):,:/;;-:Q55:ATheFunctionsoftheUbiquitin-proteasomePathwayWANGJin2chang,LIYan2ping(NanchangUniversity,FoodScienceKeyLaboratoryofMinistryofEducation,JiangxiNanchang330047PRC)Abstract:Theubiquitin-proteasomepathwayisinvolvedinthedegradationofmanyproteins.Soitregulatesmanybasiccellularprocesses,suchasantigenpresentation,signaltransduction,cellcycleandsoon,whichdealswithmanyhumanbeingsdiseases.Thereforeitprovideuswithanewideaofpreventingandcuringdiseases.Keywords:Ubiquitin,Proteasome,Ubiquitin-proteasomepathway(ubiquitinproteasomepathway;upp)ATPUPP,,Aaron,AvramIrwin320041(upp)(upp)(ubiquit2in,ub)4:(ubiquitin-activa2tingenzyme,E1)(ubiquitin-conjuga2tingenzymes,E2s)(ubiquitin-carrierprotein)-(ubiquitin-li2gatingenzymes,E3s)(proteasome),upp76,,,:3Goldstein1975©1994-2012ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(E1),E1aE1b,(E2s)2,:13,25301416KD,35%,-3--,,-,-,20s26s26s20s19s,20s,14,22,7,7777,19s1718,2,(lid),(base)10,6ATP,,8ATP,Rpn11/Pda/s13,[1]2C2:;,,:(ubiquitinC-ter2minalhydrolases(UCHs)),2030KD,C,,,(ubiquitin-spicificprote2ases-UBPs/USPs),100KD,,Doa4UPP,doa4D,,,[2]3(upp),2:,E1,76GlyCys,ATP;,,E2Cys,-;,E3,()Lys,-,,Ub7Lys,,C-Gly651200624©1994-2012ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(MHC)I,T(CTL)MCHI(MajorhistocompatibilitycomplexclassI)MCHI,T,[3]FabienpQE30,C,,,MHCI[4]SancyE6,MCHI[5]4,4,,(),,Th1[6]412UPP,,,26s,,-,-UPP,E3[7]Li-JunHuo,cyclinB1MAPK/p90rsk,[8]sunQ.Y.UPP,,1[9]413UPPUPP2:,,,,[10]1817(PD),(PD)UPP[11]4:-synu2cleinUCH-L1DJ-1parkinUPP-synucleinlewylewyparkinson,;UCH-L1;DJ-1SUMO;ParkinAlzhei2mer,[12]UPPAlzheimer,:Alzheimer;;Alzheimer;Alzheimer7512:©1994-2012ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[13]NF-kBUPPNF-kBE3RS1kB/6-TrCPIkB,26sIkBNF-kB,[14].,[15]p53,p53p53,MG132lactacystin,p53p53N,p53[16];p53,p53p300CREBp300SUMOSUMO-1p300SUMOubc9,UPP[17]UPPUPPSGC-7901DNA,G1,[18]UPPMG-132Eca9706[19](aclarubicin,ACR)(cispla2tin,CDDP1),UPP[20],:[1]Hartman-PetersenR,GordonC.Proteinsinteractingwith26sproteasome[J].CellularandMolecularlifeScience,2004,61:1589-1595.[2]SowmyaSwaminathan,AlexanderY.Amerik,etal.Thedoa4deubiquitinatingenzymeisrequiredforubiquitinhomeostasisinyeastmolecular[J].BiologyoftheCell,1999,10:2583$2594.[3]JianZhang.UbiquitinligasesinTcellactivationandautoimmunity[J].ClinicalImmunology,2004,111:234$240.[4]FabienLoison,PhilippeNizard,TonySourissean,etal.AUbiquitin-BasedAssayfortheCytosolicUptakeofProteinTransductionDomains[J].MolecularThera2py,2005,11(2):205-214.[5]SancyA.Leachman,MarkShylankerich,MartinD.slade,etal.Ubiquitin-Fusedand/orMultipleEarlyGenesfromCottontailRabbitPapillomavirusasDNAVaccines[J].JournalofVirology,2002,76(15):7616-7624.[6],,.[J].,2003,24(1):61-63.[7]ClausSchwechheimerandLuzIrinaACalderonVil2lalobos.Cullin-containingE3ubiquitinligasesinplantdevelopment[J].CurrientOpinioninPlantBiol2ogy,2004,7:677-686.[8]Li-JunHuo,Heng-YuFan,Zhi-ShengZhong,etal.Ubiquitin$proteasomepathwaymodulatesmouseoocytemeioticmaturationandfertilizationviaregula2tionofMAPKcascadeandcyclinB1degradation[J].MechanismsofDevelopment,2004,121(10):1275$1287.[9]SunQY,FuchimotoD,NagaiT.Regulatoryrolesofubiquitin-proteasomepathwayinpigoocytemeioticmaturationandfertilization[J].Theriogenology,2004,62:245-255.[10]AaronCiechanover,AlanL.Schwartz.Theubiquitinsystem:pathogenesisofhumandiseasesanddrugtar2geting[J].BiochimicaetBiophysicaActa,2004,1695:3-17.(186)851200624©1994-2012ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.=(),,,,,,,:[1],.80C196MC[J].,2003,(7):51-52.[2],,.[J].,2000,(2):7-9.[3].[J].,2001,(2):21-22.[4].[M].:,2001.(158)[11]RanjitaBetarbet,ToddB.Sherer,J.TimothyGreenamyre.Ubiquitin-proteasomesystemandParkinsonsdiseases[J].ExperimentalNeurolo2gy,2005,191(Supplement1):S17-S27.[12],.Alzheimer[J].,2003,23(8):536-538.[13]Xiao-yunWu,AlexChang,MariusSudel,etal.GeneticinteractionsbetweentheESS1prolyl-isomeraseandtheRSP5ubiquitinligaserevealop2posingeffectsonRNApolymeraseIIfunction[J].CurGenet,2001,40:234-242.[14],,.NF-kB[J].,2003,48(18):1893-1911.[15]JohnHanna,DavidS.Leggett,DanielFinley.Ubiq2uitindepletionasakeymediatoroftoxicitybytranslationalinhibitors[J].MolecularandCillularBiology,2003,23(24):9251-9261.[16],,.p53[J].,2003,10(5):465-468.[17]GirdwoodD,BumpassD,VaughanOA,etal.P300transcriptionalrepressionismediatedbySUMOmodification[J].MolCell,2003,11(4):1043-1054.[18],,,.-SGC-7901DNA[J].,2004,6(2):212-214.[19],,,.-[J].,2004,20(3):355-356.[20],,.[J].,2003,25(5):302-304.681200624©1994-2012ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.