Caspases: cellular demolition experts

Apoptosis is co-ordinated by a family of cysteine proteases, the caspases, that dismantle the cell by targeting a panoply of proteins for limited prot eolysis. The mammalian caspase family contains 14 members, a subset of whic h participates in apoptosis, with the remainder likely to be involved in th e processing of pro-inflammatory cytokines. Apical caspase activation event s are typically initiated by adaptor molecules that promote caspase aggrega tion and facilitate caspase autoactivation. In contrast, distal caspase act ivation events are controlled by caspases activated earlier in the cascade. Many cellular stresses provoke apoptosis by damaging mitochondria which re sults in the release of factors [such as cytochrome c and SMAC (second mito chondrial-derived activator of caspase)/Diablo] that trigger caspase activa tion and cell death. Here, we discuss the hierarchical nature of the caspas e cascade that is triggered upon the release of mitochondrial cytochrome c into the cytoplasm, and the role of specific caspases within this cascade i n targeting proteins for degradation. Finally, feedback amplification loops and important control points within the caspase cascade will be discussed.