Theproinflammatorycytokinetumornecrosisfactor-α(TNF-α)regulatesimmuneresponses,inflammationandprogrammedcelldeath.TheultimatefateofacellexposedtoTNF-αisdeterminedbysignalintegrationbetweenitsdownstreameffectors,includingcaspases,IKBkianse(IKK)andc-JunN-terminalproteinkinase(JNK).However,themolecularmechanismsareincompletelyunderstood.Weinvestigatedthisissueusinggeneticandbiochemicalapproaches.WeidentifiedIKKβ,acatalyticsubunitoftheIKKcomplexthatisrequiredforNF-KBactivationandcellsurvivalinresponsetoTNF-α,wasproteolyzedbycasp-3-relatedcaspases.ThisproteolysiseliminatedIKKactivityandpromotedTNF-α,killing.Point
