HUMAN CATHEPSIN-W, A PUTATIVE CYSTEINE PROTEASE PREDOMINANTLY EXPRESSED IN CD8(-LYMPHOCYTES() T)

A 750-bp fragment of a novel human cysteine protease has been identifi ed from the dbEST databank. PCR cloning and DNA sequencing yielded a 1 .38-kb full-length cDNA which encodes a polypeptide of 376 amino acids . The protein consists of a putative 21-residue signal peptide, a 106- residue propeptide and a 252-residue mature protein. The deduced amino acid sequence contains the highly conserved residues of the catalytic triad of papain-like cysteine proteases: cysteine, histidine, and asp aragine. Furthermore, the protein sequence possesses two potential N-g lycosylation sites: one in the propeptide and one in the mature protei n. Comparison of the amino acid sequence of human cathepsin W with oth er human thiol-dependent cathepsins revealed a relatively low degree o f similarity (21-31%). In contrast to cathepsins L, S, K, B, H and O, cathepsin W contains a 21-amino acid peptide insertion between the put ative active site histidine and asparagine residues and an 8-amino aci d C-terminal extension. This unique sequence may indicate that catheps in W belongs in a novel subgroup of papain-like proteases distinct fro m that of cathepsin L- and B-like proteases. Northern blot analysis in dicates a specific expression of cathepsin W in lymphatic tissues. Fur ther analysis revealed predominant levels of expression in T-lymphocyt es, and more specifically in CD8(+) cells. The expression of the prote ase in cytotoxic T-lymphocytes may suggest a specific function in the mechanism or regulation of T-cell cytolytic activity. (C) 1997 Federat ion of European Biochemical Societies.