FIGURE 2.

The mechanism of cell apoptosis. The extrinsic pathway involves the recruitment and activation of procaspase-8, and activated caspase-8 then directly activates the effector caspases such as caspase-3 to initiate the execution process. The intrinsic apoptotic pathway is mediated by the cleavage of BID (BH3 interacting domain death agonist), a BCL-2 homology 3 (BH3)-only protein. Truncated BID (tBID) subsequently translocates to the mitochondria and activates the BCL-2 family members BAX and BAK. Upon activation, BAX and BAK induce mitochondrial outer membrane permeabilization and the release of proapoptotic mitochondrial contents into the cytoplasm, such as cytochrome c. Released cytochrome c binds APAF1, and APAF-1 recruits procaspase-9 through the CARD-CARD interaction and forms the apoptosome, leading to proximity-induced activation of caspase-9, which in turn cleaves and activates effector caspases (Members of the IAP family including XIAP negatively regulate caspase activation and they can be inactivated by SMAC). APAF1, apoptotic protease activating factor-1; Bax/Bak, a proapoptotic member of Bcl-2 family; BID, BID protein; FADD, Fas associated death domain; MCLl, myeloid cell leukemia-1; MOMP, mitochondrial outer membrane permeabilization; SMAC, second mitochondria-derived activator of caspases; X1AP, X-linked inhibitor of apoptosis protein.