Figure 1.

TRAIL (TNF-related apoptosis-inducing ligand)-mediated signaling. TRAIL transduces the signals intracellularly through death receptors. Death-inducible signaling complex (DISC) is formed by the interaction of the death receptor Fas-associated protein with death domain (FADD) and pro-caspase-8. Formation of DISC is necessary for the activation of caspase-8. Caspase-8 activates its downstream effector caspase-3. However, caspase-8 may also proteolytically process Bid to initialize the intrinsic pathway. The intrinsic pathway is triggered following entry of truncated Bid into mitochondria. Cytochrome c and SMAC are released from mitochondria and an apoptosome was formed in the cytoplasm by the assembly of apoptotic protease activating factor (APAF), cytochrome c, and pro-caspase-9. The apoptosome is necessary for the activation of caspase-9 and it can further activate caspase-3 to induce apoptosis in cancer cells. In healthy cells, APAF is present as an autoinhibitory monomer. However, mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c unlocks APAF.