ROLE OF MULTIPLE CELLULAR PROTEASES IN THE EXECUTION OF PROGRAMMED CELL-DEATH

A family of mammalian homologues of the Caenorhabditis elegans cell de ath protein Ced-3 has been recently discovered. These mammalian protei ns encode novel cysteine proteases with homology to the interleukin-1 beta converting enzyme (ICE). Although several studies support a role for one or more of these proteases in mediating apoptosis, their mecha nism of action is far from understood. The presence of multiple mammal ian ICE-like proteases, with apparently similar apoptotic function ind icates that, despite its conservation during evolution, the cell death pathway is much more complex in mammals than in the worm. In addition to ICE-like proteases, several other proteases of different cleavage specificities have been implicated in apoptosis. There is now a growin g body of evidence suggesting that apoptosis involves the activation o f a cascade of proteases. This article summarises the presently availa ble evidence and discusses how multiple proteases might be required in the effector phase of cell death.