THE CYSTEINE-PEPTIDASE BLEOMYCIN HYDROLASE IS A MEMBER OF THE GALACTOSE REGULON IN YEAST

Bleomycin hydrolase is a cysteine peptidase discovered through its abi lity to detoxify the anti-cancer glycopeptide, bleomycin, Although fou nd in all tissues in mammals and in both eukaryotes and prokaryotes, t he normal cellular function of this peptidase is not known. We had pre viously reported the purification of bleomycin hydrolase hom yeast bas ed on its unexpected ability to bind DNA. Recently we collaborated in solving the crystal structure of this protein, revealing a hexameric r ing organization. We now report that the molecular characterization of the gene encoding yeast bleomycin hydrolase is also surprising. The t ranscription of the gene is regulated by galactose. Furthermore, this regulation is conveyed by a binding site for the Gal4 regulatory prote in in its promoter, prompting the designation of this gene as GAL6. Ga l6p also appears to have a negative effect on the GAL system as a dele tion of the gene leads to a 2-5-fold higher expression of the GAL1, GA L2, GAL7, and MEL1 genes. The GAL6 deletion does slat affect the expre ssion of another inducible gene, HSP26. Neither the peptidase nor the nucleic acid binding activity of Gal6p as assayed is apparently requir ed to convey this regulation, implying yet another function for this n ew member of the GAL regulon.