Identification and Mapping ofCasp7,a Cysteine Protease Resembling CPP32β, Interleukin-1β Converting Enzyme, and CED-3

Abstract

Cloning of interleukin-1β converting enzyme (ICE) andCaenorhabditis elegansdeath protein CED-3 revealed the structural and functional homology between these two proteases. It also suggested the involvement of ICE-like cysteine protease in apoptosis. Several CED-3- and ICE-like cysteine proteases have been described, including Nedd2/Ich-1, CPP32β, Tx, ICErel3, and Mch2. We have previously described a mouse ortholog of cysteine protease CPP32β that shares strong homology with ICE and CED-3. Here, we describe the cloning of mouse and humanCasp7,another member of this family of cysteine proteases. MouseCasp7encodes a putative 340-amino-acid polypeptide that contains all the known conserved residues required for protease function, including the QACRG sequence, aspartic acid residues for internal cleavage sites, and the residues required for substrate binding. Three RNA variants of humanCasp7were also cloned. Amino acid sequence analysis indicated thatCasp7shared high homology with CPP32β/Casp3 and Mch2/Casp6. Northern blot analysis demonstrated that a 2.6-kbCasp7mRNA was expressed in various tissues except brain. Mouse interspecific backcross mapping allowed localization ofCasp7to the distal region of mouse chromosome 19, linked toMxi1, Adra2a,andAop1.