Biochemical and genetic analysis of apoptosis has determined that intracellular proteases are key effectors of cell death pathways. In particular, early studies have pointed to the primacy of caspase proteases as mediators of execution. More recently, however, evidence has accumulated that noncaspases, including cathepsins, calpains, granzymes, and the proteasome complex, also have roles in mediating and promoting cell death. An important goal is to understand the importance of distinct noncaspases in various forms of apoptosis, and to determine whether pathways mediated by noncaspase proteases intersect with those mediated by caspases. In this review the roles of noncaspase proteases in the biochemistry of apoptosis will be discussed. Leukemia (2000) 14, 1695-1703.

Proteases that are members of the caspase (or interleukin-1␤cessing of interleukin-1␤. [11][12][13] Overexpression of either CED-3 converting enzyme (ICE)) protease family have been shown to or caspase-1 was found to induce apoptosis in Rat-1 fibroblast be important mediators of apoptosis induced by Fas activation, cells. 14 Recent studies have led to the identification and clonneurotrophic factor withdrawal, and detachment from extraing of at least 10 members of the caspase protease family, cellular matrix. In this report we have investigated the potential caspase-1 to caspase-10. 15,16,9 Members of this family exhibit

The molecular mechanisms responsible for induction or inhibition of apoptosis signal transduction have been intensively investigated during the past few years. Information gained from mechanistic studies and from structural analysis of apoptosis regulatory proteins has provided considerable insight into the pathways that determine whether a cell will live or die. Many of these advances were recently presented at the American