Figure 1.

Pathways for caspase activation. Two of the major pathways for caspase activation in mammalian cells are presented, the extrinsic (left) and intrinsic (right). The extrinsic pathway can be induced by members of the TNF family of cytokine receptors, such as TNFR1 and Fas. These proteins recruit adapter proteins to their cytosolic DDs, including Fadd, which then binds DED-containing pro-caspases, particularly pro-caspase-8. The intrinsic pathway can be induced by release of cytochrome c from mitochondria, induced by various stimuli, including elevations in the levels of pore-forming pro-apoptotic Bcl-2 family proteins such as Bax. In the cytosol, cytochrome c binds and activates Apaf-1, allowing it to bind and activate pro-caspase-9. Active caspase-9 (intrinsic) and caspase-8 (extrinsic) have been shown to directly cleave and activate the effector protease, caspase-3. Other caspases can also become involved in these pathways (not shown); thus, the schematic represents an oversimplification of the events that occur in vivo.