Proposed model: calpain-mediated cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like cysteine protease may rapidly degrade p18 Bax. Although full-length p21 Bax can initiate apoptosis through the mitochondrial pathway, p18 Bax is more potent than WT p21 Bax in disrupting mitochondrial integrity and inducing apoptosis. Therefore, calpain-mediated cleavage of Bax to p18 Bax functions as an amplification step that accelerates the apoptotic process following cytotoxic stress. On the other hand, removal of the N-terminal domain of Bax facilitates the rapid degradation of p18 Bax by a cathepsin-like cysteine protease. This specific proteolytic degradation of p18 Bax may be equivalent to a silencing mechanism for this potent form of Bax to delay cell death or promote survival. Thus, in addition to the executionary consequences of caspase activation, noncaspase cysteine proteases such as calpain and the cathepsin-like protease may be involved in regulating apoptosis through sequential proteolytic processing of Bax and p18 Bax.