NF-κB信号转导途径研究进展

NF2B1112(11;21):NF2B,NF2B:;NF2B;;:Q753:A:100623730(2002)0520260203NF2B,,,NF2B1NF2B111NF2B/Rel[1]NF2B/Bel,NF2B1(p50)NF2B2(p52)RelA(p65)RelBc2RelN300Rel(RelHomologyDomain,RHD),DNA(nucleartranslocationsignal,NLS),DNABNF2B(IB)RelARelBc2RelC(transactivationdomain),Ser,p50p52p50p52p105p100C,(ankyrinre2peatmotif),ATP,p50p521NF2B/Relp50p52RelARelBc2Relp105p100p50p50/p50p50/p52p50/RelAp50/RelBp50/c2Relp52p52/p52p52/RelAp52/RelBp52/c2RelRelARelA/RelARelA/c2Relp105/RelAp100/RelARelBp105/RelBp100/RelBc2Relc2Rel/c2Relp105/c2Relp100/c2RelNF2B/Rel1p50/RelA(NF2B),,,B,10-12Mp50B,RelA:(1)C;(2)IBRel,,NF2B/RelIB,RelB,NF2BNF2B/Rel,B,,,:(1)B,p50/RelAB5GGGRNNYYCC3,RelA/c2RelB5HGGARRNYYCC3(HACT,R,Y);(2)B,;(3);(4);(5)IB,,B,112IB[2]IB8,p100p105IBIBIBIBBcl23IB2R:IBC38,33,NF2BRHDN,Ser,IBIBNF2B/Rel,IBIBc2RelRelA,IBp65/p65c2Rel/c2Rel,Bcl23p52/p52p50/p50,IBNF2BDNAIBIBIBNF2B/Rel,113IKK[2]IB(IBkinase,IKK)IKK85kD,745;IKK87kD,756IKKIKK52%,N,C,IKKIKKIBSer,IBIKKIKK,IKKIKKIKKC2NF2BNF2B,NF2B206220022352NF2B(TNF)(TNF)1(IL21)2(IL22)17(IL217)(GM2CSF)(NGF)(PDGF)M3(CD3)4(CD4)28(CD28)40(CD40)(H2O2)(AT2)B4(LPS)B(TSST)1(HIV21)T(HTLV21)(CMV)EB(EBV)RNAHTLV21(PMA)A(ConA)(CrCoNi)3NF2B311IBSer1(TNFIL21),,NF2B(NIK)NIKIB(IKK),IKKp50/p65/IBIBSer32Ser36[1](,IB,IKKSer19Ser23[3];IB,IKKSer157Ser161[4])IB,IBNLys21Lys22(ubiquitin)IB,ATP26S,IB2NF2B,,p50RHD(NLS)B,,TNF[3]IL21[3]A20[5][6]:(1),5minNF2B(2),,1NF2BIBSer312IBTyr(oxidativestress)NF2B,IBSer,IBTyr,ROS(2)[7]31211Ras2MAPKNF2B(,LPS)ROS,(TK),TKTyrSH2SHC,SHCTyr,2(GRB2),Ras2GTP(SOS)SHC,SOSGTP/GDPRasRaf21(MAPKKK,)MAPKK()MAPK(),S6(p90rsk),S6IB(IKK),IKBTyr42,IB,NF2B,,DNAB,[8]2NF2BIBTyr[8]:(1),24hNF2B(2),31212PTK/PLC/NF2B[9],RTK/PLC,3(IP3)(PKC)Ca2+NF2B313p105NF2B[1]IB,p50p105,p105/p65,TNF,TPL22(tumorprogressionlocus2kinase),p105/p65p105,p50/p65,,4NF2B411,,NF2BTNFIL21,LPSIL21IBNF2B,:IB,IB,IBNF2B,NF2BNLS,NF2BIB,NF2B412162200223541211IB[11]IBB,NF2BIB,IB,NF2B,NF2B;,,NF2BIB41212p105[15]p105B,NF2Bp105,p105,p50,p50/p50p50/p50B,NF2B41213A20A20(Zincfin2gerproteinA20,A20)NF2BMarrcoK[10]A20B,A20NF2BLeeEG[11]A20,A20TNFNF2B,TNFLPS,,A20TNF(TRAFs)[12]NF2B(A202bindinginhibitorsofNF2Bactivation,ABINs)[13]IKK2[14],,NF2B5NF2B,,NF2BIBNF2B,,,,NF2B,,,NF2B,1SuzukiT.RoleofNF2BinMacrophageActivation(review)InEndotoxininHealthandDiseaseedsbyDCMorrison,HBrade,SOpalandSvogel[M].MarcelDekker,NYN.Y,1999,5022520.2JangIL,PharmD,GilbertJB,etal.NuclearfactorKappaBimportanttranscriptionfactorandtherapeutictarget[J].JClinPharmacol,1998,38:9812993.3MercurioF,ZhuH,MurrayDw,etal.IKK21andIKK22:Cytokine2activatedIkappaBkinaseessentialforNF2Bactiva2tion[J].Science,1997,287:8602866.4WhitesideST,EpinatJC,RiceNR,etal.IkappaBepsilon,anovelmemberoftheIkappaBfamily,controlsRelAandcRelNF2kappaBactivity[J].EMBOJ,1997,16:141321426.5RudiB,KarenH,SofieVH,etal.A20andA202bindingproteinascellularinhibitorsofnuclearfactor2B2dependentgeneexpressionandapoptosis[J].BiochemPharmacol,2000,60(8):114321151.6RobertsML,CowsertLM.Interleukin21betaandreactiveoxygenspeciesmediateactivationofc2junNH22terminalki2nas,inhumanepithelialcells,bytwoindependentpathways[J].BiochemBiophysResCommun,1998,251:1662172.7JianpingY,MinD,XiaoyingI,etal.Ontheroleofhydrox2ylradicalandtheeffectoftetrandrineonnuclearfactor2Bac2tivationbyphorbol122myristate132acetate[J].AnnalsofClinicalandLaboratoryScience,2000,30(1):65271.8AndrewB,LukeAJ.Oxidativestressandnuclearfactor2Bactivation[J].BiolPharmacology,2000,59:12223.9SergeyAT,KevinNP,AliciaAS,etal.ProteinkinaseCandcalcineurinsynergizetoactivateIBkinaseandNF2BinTlymphocytes[J].JBiolChem,1997,274(33):22923222931.10MarcoK,SofieVH,KarenH,etal.FunctionalredundancyofthezincfingersofA20forinhibitionofNF2Bactivationandprotein2proteininteractions[J].FEBSLett,2001,498:93297.11LeeEG,BooneDL,ChaiS,etal.FailuretoregulateTNF2inducedNF2BanddeathresponsesinA20deficientmice[J].Science,2000,289:235022354.12ArchRH,GedrichRW,ThompsonCB.Tumornecrosisfac2torreceptor2asociatedfactors(TRAFs)2familyofadapterproteinsthatregulateslifeanddeath[J].GeneDev,1998,12:282122830.13VanHS,DelaeiF,HeyninckK,etal.Identificationofanov2elA202bindinginhibitorofnuclearfactor2kappaBactivationtermedABIN22[J].JBiolChem,2001,10;276(32):30216230223.14ZhangSQ,KovalenkoA,CantarellaG,etal.RecritmentoftheIKKsignalosometothep55TNFreceptor:RIPandA20bindtoNEMO(IKK)uponreceptorstimulation[J].Immu2nity,2001,12:3012311.(20012042262002205208):(259)IkappaBepsilon,anovelmemberoftheIBfamily,con2trolsRelAandcRelNF2Bactivity[J].EMBOJ,1997,16:141321426.10CogswellPC,GuttridgeDC,FunkhouserWK,etal.Selectiveacti2vationofNF2kappaBsubunitsinhu2manbreastcancer:potentialrolesforNF2kappaB2/p53andforBcl23[J].Oncogene,2000,19:112321131.11MalininNL,BoldinMP,KovalenkoAV,etal.MAPK32relatedkinasein2volvedinNF2BinductionbyTNF,Cd95andIL21[J].Nature,1997,385:5402543.12MichaelJ,May,SankarGhosh,etal.IBkinases:Kinsmenwithdifferentcrafts[J].Science,1999,284:2712273.13KwakYT,GuoJ,ShenJ,etal.AnalysisofdomainsintheIKK(alpha)andIKK(beta)proteinsthatregulatetheirkinaseactivity[J].JBiolChem,2000,275:34060234067.14LingL,CaoZ,GoeddelDV.NF2kap2paB2inducingk