Figure 2. Schematic of caspase signaling pathway.

The extrinsic pathway is initiated by biding of death ligands such as TNF-α and Fas ligand to their cell-surface death receptors such as TNFR and Fas. The death domains of these receptors recruit adaptor molecules like FADD and caspase-8, which leads to the activation of caspase-8. Activated caspase-8 cleaves the effector caspases such as caspase-3, thereby activating them and inducing apoptosis. The extrinsic pathway interacts with the intrinsic pathway via caspse-8-mediated cleavage of Bid. The intrinsic pathway is initiated by release of mitochondrial intermembrane proteins such as cytochrome c and Smac/Diablo into the cytosol. Released cytochrome c forms an apoptosome with Apaf-1 and caspase-9, which leads to caspase-9 activation. Smac/Diablo enhances caspase activation through the neutralization of IAP proteins.