IDENTIFICATION AND MAPPING OF CASP7, A CYSTEINE PROTEASE RESEMBLING CPP32-BETA, INTERLEUKIN-1-BETA CONVERTING-ENZYME, AND CED-3

Cloning of interleukin-1 beta converting enzyme (ICE) and Caenorhabdit is elegans death protein CED-3 revealed the structural and functional homology between these two proteases. It also suggested the involvemen t of ICE-like cysteine protease in apoptosis. Several CED-3- and ICE-l ike cysteine proteases have been described, including Nedd2/Ich-1, CPP 32 beta, Tx, ICE(rel)3, and Mch2. We have previously described a mouse ortholog of cysteine protease CPP32 beta that shares strong homology with ICE and CED-3. Here, we describe the cloning of mouse and human C asp7, another member of this family of cysteine proteases. Mouse Casp7 encodes a putative 340-amino-acid polypeptide that contains all the k nown conserved residues required for protease function, including the QACRG sequence, aspartic acid residues for internal cleavage sites, an d the residues required for substrate binding. Three RNA variants of h uman Casp7 were also cloned. Amino acid sequence analysis indicated th at Casp7 shared high homology with CPP32 beta/Casp3 and Mch2/Casp6. No rthern blot analysis demonstrated that a 2.6-kb Casp7 mRNA was express ed in various tissues except brain. Mouse interspecific backcross mapp ing allowed localization of Casp7 to the distal region of mouse chromo some 19, linked to Mxi1, Adra2a, and Aop1., (C) 1997 Academic Press.