CALPAIN AND CELL-DEATH

Neither the early nor the late steps in apoptosis have been defined bi ochemically. Several different signalling pathways have been implicate d, and these are familiar from other signalling paradigms. In what way could they lead to cell death, when under the usual conditions they a re involved in reversible activation events? A possible role for prote olysis is suggested, because the cleavage of a peptide bond is one of the few irreversible processes in cellular metabolism, and death, afte r all, is an irreversible outcome, In this review Me discuss the calci um-dependent neutral protease calpain, a member of the papain family o f cysteine proteases quite distinct from the ICE family. Calpain has b een shown to play an essential role in several important examples of p hysiologic apoptosis, It seems to play its part after the various 'pri vate' pathways have been invoked, but before the final common pathway.