ABSTRACT
Apoptosis is a regulated program of cellular suicide with profound effects on the development and homeostasis of multicellular organisms (Rudin and Thompson, 1997; Steller, 1995; Jacobson et al., 1997). Researchers have ascribed neurodegenerative conditions, various forms of cancer, and AIDS to a deregulation of programmed cell death (Rudin and Thompson, 1997). A variety of apoptotic signals induce distinct biochemical and morphological changes in mammalian cells that accompany the controlled disassembly of cellular structures (Green and Reed, 1998). In particular, the sequential proteolytic maturation of a cascade of aspartate-specific cysteine proteases (caspases) appears crucial for the execution of the apoptotic program (Thornberry and Lazebnik, 1998; Green, 1998). The endoproteolytic activity of mature caspases is limited by strict tetrapeptide sequence specificity (Thornberry et al., 1997; Thornberry and Lazebnik, 1998). Nevertheless, substrate cleavage results in the inactivation of proteins with critical functions in the maintenance of nuclear architecture, the repair of damaged DNA or
mRNA splicing; and the activation of pro-apoptotic functions such as Bid, a Bcl-2 family member, other caspases, and DNA fragmentation factor (Thornberry et al., 1997; Thornberry and Lazebnik, 1998; Cohen, 1997).
