Fig. 2.

Signaling pathway of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL interacts with death receptor 5 or 4 (DR5, DR4, respectively) on the cell surface and forms a protein complex termed death-inducing signaling complex (DISC) that contains the FAS-associated death domain protein (FADD) and pro-caspase-8 or -10. The activated caspase-8 or -10 then cleaves and activates caspase-3 and the bcl-2 interacting domain (Bid). Bid stimulates mitochondria and activates caspase-9, and the activated caspase-9 cleaves and activates caspase-3. Activated caspase-3 cleaves many substrates, resulting in apoptosis. Decoy receptor 1 and 2 (DcR1, DcR2, respectively) and osteoprotegerin (OPG) have dominant negative functions and block TRAIL-induced apoptosis