Apoptosis

Apoptosis plays a critical role during normal development and homeostasis of adult tissues. Consequently, deregulation of apoptosis is associated with numerous diseases ranging from cancer to neurodegeneration. In this article, we describe in biochemical and structural detail the mechanisms that mediate the activation of cysteinyl aspartate-specific proteases (caspases) within large multimeric complexes following the stimulation of death receptors and/or the perturbation of various intracellular organelles. In doing so, we discuss those factors that directly or indirectly regulate the activation (or activity) of caspases, including pro- and antiapoptotic BCL-2 family members, inhibitor of apoptosis (IAP) proteins, and IAP antagonists. We also briefly discuss highly related protein complexes that mediate an alternative form of cell death in cells lacking caspase activity.