Molecular cloning and structural and functional characterization of human cathepsin F, a new cysteine proteinase of the papain family with a long propeptide domain

A cDNA encoding a new cysteine proteinase belonging to the papain family an d called cathepsin F has been cloned from a human prostate cDNA library. Th is cDNA encodes a polypeptide of 484 amino acids, with the same domain orga nization as other cysteine proteinases, in; eluding a hydrophobic signal se quence, a prodomain, and a catalytic region. However, this propeptide domai n is unusually long and distinguishes cathepsin F from other proteinases of the papain family. Cathepsin F also shows all structural motifs characteri stic of these proteinases, including the essential cysteine residue of the active site. Consistent with these structural features, cathepsin F produce d in Escherichia coli as a fusion protein with glutathione S-transferase de grades the synthetic peptide benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoum arin, a substrate commonly used for functional characterization of cysteine proteinases, Furthermore, this proteolytic activity is blocked by transepo xysuccinyl-L-leucylamido-(4-guanidino an inhibitor of cysteine proteinases. The gene encoding cathepsin F maps to chromosome 11q13, close to that enco ding cathepsin W, Cathepsin F is widely expressed in human tissues, suggest ing a role in normal protein catabolism. Northern blot analysis also reveal ed a significant level of expression in some cancer cell lines opening the possibility that this enzyme could be involved in degradative processes occ urring during tumor progression.