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

A family of mammalian homologues of the Caenorhabditis elegans cell death protein Ced-3 has been recently discovered. These mammalian proteins 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 mechanism of action is far from understood. The presence of multiple mammalian ICE-like proteases, with apparently similar apoptotic function indicates 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 growing body of evidence suggesting that apoptosis involves the activation of a cascade of proteases. This article summarises the presently available evidence and discusses how multiple proteases might be required in the effector phase of cell death.