Proteolytic regulation of apoptosis

Much of the proteolysis that occurs during apoptosis is directed by caspase s, a family of related cysteinyl proteases. A relatively small number of ce llular proteins are targeted by caspases, yet their function is dramaticall y affected and apoptosis is triggered. Other proteases, such as granzymes a nd calpain, are also involved in the apoptotic signaling process, but in a much more cell type- and/or stimulus type-specific manner. At least three d istinct caspase-signaling pathways exist; one activated through ligand-depe ndent death receptor oligomerization, the second through mitochondrial disr uption, and the third through stress-mediated events involving the endoplas mic reticulum. These pathways also appear to interact to amplify weak apopt otic signals and shorten cellular execution time. Finally, defects in caspa ses contribute to autoimmune disease, cancer and certain neurological disor ders.