A JNK-Dependent Pathway Is Required for TNFα-Induced Apoptosis

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1、Cell,Vol.115,61–70,October3,2003,Copyright2003byCellPressAJNK-DependentPathwayIsRequiredforTNF
-InducedApoptosisYibinDeng,1XiaoyangRen,1LinYang,YahongLin,TNF
-mediatedapoptosis(DeSmaeleetal.,2001;TangandXiangweiWu*etal.,2001).DespitethefactthatsustainedactivationHuffingtonCenteronAgingandDepart

2、mentofofJNKpromotescelldeath,themolecularbasisofhowMolecularandCellularBiologyJNKcontributestoTNF
-mediatedapoptosisremainsBaylorCollegeofMedicinetobeaddressed.Houston,Texas70030Theintrinsicapoptoticpathwayistheresultofactiva-tionofmitochondria-mediatedcelldeathevents,includ-ingchangesinmitochon

3、drialmembranepermeabilitySummaryandsubsequentreleaseofproapoptoticfactorsin-volvedinvariousaspectsofapoptosis(Wang,2001).Tumornecrosisfactor(TNF
)receptorsignalingcanThereleasedfactorsincludecytochromec(cytoc;Liusimultaneouslyactivatecaspase8,thetranscriptionetal.,1996a),apoptosisinducingfactor(

4、AIF)(Susinetfactor,NF-Bandthekinase,JNK.Whileactivationofal.,1999),secondmitochondria-derivedactivatorofcas-caspase8isrequiredforTNF
-inducedapoptosis,pase(SmacorDIABLO)(Duetal.,2000;VerhagenetandinductionofNF-Binhibitscelldeath,thepreciseal.,2000),Omi/HtrA2(Suzukietal.,2001),andendonu-functio

5、nofJNKactivationinTNF
signalingisnotcleaseG(Lietal.,2001).CytosoliccytocandApaf-1clearlyunderstood.Here,wereportthatTNF
-medi-formanessentialpartofapoptosiscomplexandleadatedcaspase8cleavageandapoptosisrequirease-totheactivationofcaspase9,whichthenprocessesandquentialpathwayinvolvingJNK,Bid,andS

6、mac/DIA-activatesothercaspasestoorchestratethebiochemicalBLO.ActivationofJNKinducescaspase8-independentexecutionofcells(Lietal.,1997).cleavageofBidatadistinctsitetogeneratetheBidAlthoughtheapoptoticpathwaysthroughdeathre-cleavageproductjBid.TranslocationofjBidtomito-ceptorsandmitochondriaarecapa

7、bleofoperatinginde-chondrialeadstopreferentialreleaseofSmac/DIABLO,pendently,accumulatingevidencesuggeststhatabutnotcytochromec.ThereleasedSmac/DIABLOthencrosstalkexistsbetweenthetwopathways.OnelinkdisruptstheTRAF2-cIAP1comp