FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2

Apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO-2L) has been shown to exert important functions during v arious immunological processes. The involvement of the death adaptor protei ns FADD/MORT1,TRADD, and RIP and the apoptosis-initiating caspases-8 and -1 0 in death signaling by the two death-inducing TRAIL receptors 1 and 2 (TRA IL-R1 and TRAIL-R2) are controversial. Analysis of the native TRAIL death-i nducing signaling complex (DISC) revealed ligand-dependent recruitment of F ADD/MORT1 and caspase-8. Differential precipitation of ligand-stimulated TR AIL receptors demonstrated that FADD/MORT1 and caspase-8 were recruited to TRAIL-R1 and TRAIL-R2 independently of each other. FADD/MORT1- and caspase- 8-deficient Jurkat cells expressing only TRAIL-R2 were resistant to TRAIL-i nduced apoptosis. Thus, FADD/MORT1 and caspase-8 are essential for apoptosi s induction via TRAIL-R2.