BAP1 - A NOVEL UBIQUITIN HYDROLASE WHICH BINDS TO THE BRCA1 RING FINGER AND ENHANCES BRCA1-MEDIATED CELL-GROWTH SUPPRESSION

We have identified a novel protein, BAP1, which binds to the RING fing er domain of the Breast/Ovarian Cancer Susceptibility Gene product, BR CA1, BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase , suggesting that deubiquitinating enzymes may play a role in BRCA1 fu nction, BAP1 binds to the wild-type BRCA1-RING finger, but not to germ line mutants of the BRCA1-RING finger found in breast cancer kindreds, BAP1 and BRCA1 are temporally and spatially coexpressed during murine breast development and remodeling, and show overlapping patterns of s ubnuclear distribution, BAP1 resides on human chromosome 3p21.3; intra genic homozgyous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines, BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiqui tin carboxy-terminal hydrolase to be identified, BAP1 may be a new tum or suppressor gene which functions in the BRCA1 growth control pathway .