Seeonlineversionforlegendandreferences.1192Cell143,December23,2010©2010ElsevierInc.DOI10.1016/j.cell.2010.12.004SnapShot:ExtrinsicApoptosisPathwaysIngeVerbrugge,RickyW.Johnstone,andMarkJ.SmythResearchDivision,ThePeterMacCallumCancerCentre,St.AndrewsPlace,EastMelbourne3002,Victoria,AustraliaSurvivalDEDDEDComplexIIcIAPantagonists??Caspase8/10ApoptosisCaspase-independentdeath(necrosis)DEDDEDDDDEDDEDDEDDEDDEDDEDDDDEDDDDEDDEDDEDDEDDEDDDDDDDDDDDDDDDDEDDEDDDDEDDEDDEDDEDDDDEDDEDDEDDDDDDDDDDDDEDDDDDDDDDDDDEDDEDDEDDEDDDDEDDEDDEDDDDDDDDDDDDDDEDcIAP1/2cIAP1/2DDDDDDDDDDXRIPK1FADDMEMBRANECYTOPLASMProcaspase8/10cFLIPCD95LCD95ComplexIIandcIAPsindeathreceptorsignalingDEDDEDDEDDEDDEDDEDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDEDDEDDEDDEDDEDDEDDDDDBcl-2Apaf-1Procaspase9CytochromecSmac/DIABLOBakBaxO-glycosylationO-glycosylationDynaminDynaminMitochondrionMitochondrionBidCaspase8/10Procaspase8/10Procaspase8/10DeathdomainDeatheffectordomainDISCDISCMEMBRANECYTOPLASMLipidraft(SPOTS)cFLIPcFLIPCD95LTRAILProapoptoticsignalingpathwaysincludingtheraputicinterventionstrategiesDeathreceptoragonistsrhTRAIL(AMG951)a-TRAIL-R1/R2agonisticmAbs(Mapa-/Lexatumumab,Apomab,AMG655,PRO95780)rhCD95L(APO010)AnticancertherapeuticsdownregulatingcFLIPIonizingradiation,Etoposide,Vorinostat,Panobinostat,CompoundC,etc.Bcl-2antagonistsABT263,AT101,Obatoclax,OblimersemSmacmimeticsTL32711,AEG40826,LBW242,Compound3,8,11,CXIAPantisenseAEG35156tBidApoptosomeTypeITypeIIXIAPXIAPBcl-2Survival/MigrationPI3KSrcfamilykinasesCaspase8MEKK1(MAPK)MKK4,7IKK?AKTNF-κB(c-Rel)NF-κB(RelA)AP-1p38JNKSrcERKOther?DeathInflammationProliferation/SurvivalSurvivalDeathTumorpromotionTumorpromotion(invasivenessMetsformation)CD95LCD95CD95TRAILTRAIL-R1/R2TRAIL-R1/R2AntiapoptoticpathwaysactivatedbydeathreceptorsCaspase10TRADDTRAF-2Procaspase3/6/7Caspase3/7ApoptosisCaspase6Caspase3Caspase9DEDDEDDeatheffectordomainLipidraft(SPOTS)PADEDDEDDEDDEDDISCPAPADISCDEDDEDDEDDEDDEDDEDO-glycosylationO-glycosylationO-glycosylationO-glycosylationO-glycosylationO-gl...
