Caspases

Literature References: Class of cysteine proteases present as inactive zymogens (procaspases) in cytosol of healthy cells. Activated during apoptosis to cleave specific protein targets, usually after aspartic acid residues, leading to organized cellular destruction. At least 14 distinct mammalian caspases have been identified. Apoptotic caspases are divided into two categories, initiator caspases: caspase-2, -8, -9, and -10, and effector caspases: caspase-3, -6, and -7. Caspase-1, and likely caspases-4, -5, -11 and -12, are cytokine activators, responsible for generation of inflammatory response. Identification of interleukin-1b-converting enzyme (caspase-1) as a cysteine protease: N. A. Thornberry et al., Nature 356, 768 (1992). Isolation and apoptotic role of CED-3, a caspase homolog from Caenorhabditis elegans: J. Yuan et al., Cell 75, 641 (1993). Nomenclature: E. S. Alnemri et al., Cell 87, 171 (1996). Substrate specificites: N. A. Thornberry et al., J. Biol. Chem. 272, 17907 (1997). Induced proximity activation mechanism: G. S. Salvesen, V. M. Dixit, Proc. Natl. Acad. Sci. USA 96, 10964 (1999). Analysis of active sites: D. Chéreau et al., Biochemistry 42, 4151 (2003). Review of role in apoptosis: N. A. Thornberry, Y. Lazebnik, Science 281, 1312-1316 (1998); V. Cryns, J. Yuan, Genes Dev. 12, 1551-1570 (1998); of mammalian caspases: W. C. Earnshaw et al., Annu. Rev. Biochem. 68, 383-424 (1999); of activation pathways: I. Budihardjo et al., Annu. Rev. Cell Dev. Biol. 15, 269-290 (1999); of structure, function and inhibition: J.-B. Denault, G. S. Salvesen, Chem. Rev. 102, 4489-4499 (2002); of mechanisms of activation and inhibition: Y. Shi, Mol. Cell 9, 459-470 (2002); of apoptotic role in neurodegenerative diseases: R. M. Friedlander, N. Engl. J. Med. 348, 1365-1375 (2003).