Caspase-3

Literature References: Primary effector caspase required for certain distinctive biochemical and morphological events in cells undergoing apoptosis. Necessary for the dATP/cytochrome c, q.v., inducible cleavage of many cellular targets, including activation of an endonuclease, caspase-activated DNase (CAD), that is responsible for DNA fragmentation. CAD activation is achieved by caspase-3 cleavage and inactivation of the inhibitor of CAD (ICAD). Synthesized as a 32 kDa inactive zymogen, procaspase-3, that is activated by a proteolytic event generating a heterodimer consisting of a 20 kDa (N-terminal) and a 12 kDa (C-terminal) subunit. Identification: T. Fernandes-Alnemri et al., J. Biol. Chem. 269, 30761 (1994). Identification of poly(ADP-ribose) polymerase (PARP)-cleaving activity: M. Tewari et al., Cell 81, 801 (1995); and characterization of caspase-3: D. W. Nicholson et al., Nature 376, 37 (1995). Role in Fas-mediated apoptosis: J. Schlegel et al., J. Biol. Chem. 271, 1841 (1996). Crystal structure in complex with a tetrapeptide inhibitor: P. R. E. Mittl et al., ibid. 272, 6539 (1997). Cleavage of ICAD: H. Sakahira et al., Nature 391, 96 (1998); and activation of DNA fragmentation: B. B. Wolf et al., J. Biol. Chem. 274, 30651 (1999). Role in the execution phase of apoptosis: R. U. Jänicke et al., ibid. 273, 9357 (1998); E. A. Slee et al., ibid. 276, 7320 (2001). Effect of pH, ionic charge, and osmolality on activity: M. S. Segal, E. Beem, Am. J. Physiol. Cell Physiol. 281, C1196 (2001). Fluorescence studies characterizing the active site: M. Kyoung et al., Biochim. Biophys. Acta 1598, 74 (2002). Review of role in apoptosis: A. G. Porter, R. U. Jänicke, Cell Death Differ. 6, 99-104 (1999).