THE CAENORHABDITIS-ELEGANS CELL-DEATH PROTEIN CED-3 IS A CYSTEINE PROTEASE WITH SUBSTRATE SPECIFICITIES SIMILAR TO THOSE OF THE HUMAN CPP32PROTEASE

The Caenorhabditis elegons cell-death gene ced-3 encodes a protein sim ilar to mammalian interleukin-1 beta-converting enzyme (ICE), a cystei ne protease implicated in mammalian apoptosis. We show that the full-l ength CED-3 protein undergoes proteolytic activation to generate a CED -3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. We developed an easy and general method for the purification of CED-3/ICE-like proteas es and used this method to facilitate a comparison of the substrate sp ecificities of four different purified cysteine proteases. We found th at in its substrate preferences CED-3 was more similar to the mammalia n CPP32 protease than to mammalian ICE or NEDD2/ICH-1 protease. Our re sults suggest that different mammalian CED-3/ICE-like proteases may ha ve distinct roles in mammalian apoptosis and that CPP32 is a candidate for being a mammalian functional equivalent of CED-3.