A
cDNA encoding human
bleomycin hydrolase, a member of the
cysteine proteinase family of
proteins, has been cloned from a human brain cDNA library. The isolated
cDNA contains an open reading frame coding for a
polypeptide of 456
amino acids that contains all of the structural features characteristic of
cysteine proteinases, including the
cysteine,
histidine, and
asparagine residues that are essential for the catalytic properties of these
enzymes. The deduced amino acid sequence for human
bleomycin hydrolase shows 92, 40, and about 35% of identities with those determined for rabbit
bleomycin hydrolase, yeast
bleomycin hydrolase, and bacterial
aminopeptidase C, respectively. Northern blot analysis of
poly(A)+ RNAs isolated from a variety of human tissues demonstrated that human
bleomycin hydrolase is expressed in all examined tissues, which is consistent with a putative role of this
protein as a
proteolytic enzyme involved in norman cellular protein degradation and turnover. Preliminary expression analysis of
bleomycin hydrolase in different human
tumors showed increased expression of the
enzyme in a series of head and neck
carcinomas when compared with paired adjacent normal mucosa. We also observed a variable degree of
bleomycin hydrolase expression in different types of
lymphoma, with low or undetectable levels in
Hodgkin's disease samples and higher levels in Burkitt's
lymphomas. These results are consistent with a proposed role for human
bleomycin hydrolase in resistance of some
tumor to
bleomycin chemotherapy.