PATHWAYS KEY:
Apoptosis, or programmed cell death, is a regulated physiological process leading to cell death characterized by cell shrinkage, membrane blebbing and DNA fragmentation. Caspases, a family of cysteine proteases, are central regulators of apoptosis. Initiator caspases (including 8, 9, 10 and 12) are closely coupled to pro-apototic signals. Once activated, these caspases cleave and activate downstream effector caspases (including 3, 6 and 7) which in turn cleave cytoskeletal and nuclear proteins and induce apoptosis. Cytochrome C released from mitochondria is coupled to the activation of caspase 9, a key initiator caspase. Pro-apoptotic stimuli include the FasL, TNF, DNA damage and ER stress. Fas and the TNFR activate caspases 8 and 10; DNA damage leads to the activation of caspase 9; and ER stress leads to the calcium-mediated activation of caspase 12. Anti-apoptotic ligands including growth factors and cytokines activate AKT and p90RSK, which inhibit Bad and prevent cytochrome C release. TNFR can also stimulate an anti-apoptotic pathway by inducing IAP, which directly inhibits caspases 3, 7 and 9.
