BAP1 - A Novel Enzyme Associated With Regulation of BRCA1

Inventors: Frank J. Rauscher, III, and David Jensen

Tech ID: RF-96001

Description: Germ line mutations in BRCA1, the breast/ovarian cancer susceptibility gene, appear to account for about 50% of familial breast cancers. Women in families with BRCA1 mutations show a lifetime risk of 40-50% for ovarian cancer and >80% for breast cancer. However, BRCA1 mutations have not been found in sporadic, non-inherited, breast cancer and are extremely rare in sporadic ovarian cancer. Thus, other genes (and the proteins they encode) are indicated in breast cancer susceptibility. Primary candidates for these genes/proteins are those which interact with the BRCA1 protein.

Wistar researchers have identified a novel protein, BRCA1-Associated Protein-1 (BAP1) which interacts with the wild-type BRCA1, but not with some mutant BRCA1 found in patients at risk for familial breast cancer. BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase (UCH). Regulated addition and removal of ubiquitins from proteins play a role in almost every cellular growth, differentiation and homeostatic process.

The BAP1 gene is located on chromosome 3p21, near a "hot spot" for deletions and mutations in several cancers, including breast and lung. Mutations in BAP1 have been found in non-small cell lung cancers. Data to date indicate that BAP1 may be involved in either the degradation of BRCA1 or regulation of its function. BAP1 is the newest member of the UCH family and is the first nuclear-localized UCH. Thus, BAP1 considerably expands the potential roles of this family of enzymes. These findings suggest that BRCA1 may be a direct substrate for the UCH activity of BAP1, and that de-ubiquitination results in the stabilization of BRCA1.

Key Words: Diagnostic, therapeutic, antibody, DNA probe, marker, immunoassay, cancer, gene therapy, breast cancer

Applications and Advantages: BAP1 is a potential target for the development of diagnostic and therapeutic (especially small molecule) agents for breast, ovarian, lung and other tumors. Antibodies to BAP1 may be useful in the diagnosis or staging of tumors. Additionally, the BAP1 enzyme may be used in gene therapy or to develop novel therapeutic agents.

Intellectual Property Status: U.S. patent 6,307,035 and published International patent application number PCT/US97/13864.

Licensing Opportunity: Wistar is seeking licensees and/or sponsored research support to further develop and commercialize this technology.

Contact:

Meryle J. Melnicoff
Director, Business Development
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104
Phone: (215) 898-0049
Fax: (215) 573-2456
melnicoff@wistar.org

Last Updated: Aug-02