Figure 2.
Role of XIAP in the extrinsic and intrinsic cell death signaling pathways. Two different pathways can initiate apoptosis. The death-receptor mediated (extrinsic) pathway involves the activation of caspase-8 following stimulation of the receptor by ligands such as Fas. The mitochondrial (intrinsic) pathway is initiated by a variety of stimuli including DNA damaging agents such as UV and chemotherapy resulting in the mitochondrial release of cytochrome c and subsequent activation of caspase-9. Both pathways converge to activate caspases- 3 and -7, effector caspases responsible for the death of the cell. XIAP regulates both pathways by its ability to directly bind and inhibit caspase-3, -7 and -9. The mitochondrial proteins, Smac and Omi, antagonize the caspase inhibitory properties of XIAP.