Fig 1.

The TRAIL signaling pathway. The TRAIL ligand binds to functional receptors DR4 and DR5 and non-signaling receptors OPG (not shown), DcR1 and DcR2. Binding of TRAIL ligand or receptor-specific agonistic antibodies to DR4 and DR5 induces trimerization of the receptors. The cytoplasmic part of the DR4 and DR5 receptors contain death domains (DD) that enable recruitment of Fas associated protein with death domain (FADD) and procaspase 8 (proCASP8), enabling cleavage and activation of proCASP8 to its active form caspase 8 (CASP8). CASP8 activates downstream effector caspases both directly and, in some cells, through activation of the mitochondrial apoptosis pathway through BID cleavage. Once activated, effector caspases cleave downstream substrates and induce DNA fragmentation, ultimately leading to apoptosis. For additional details, please refer to the text.