BRCC36, A Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex, Candidates for BRCA3
Abstract
Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among nonBRCA1 and BRCA2 breast cancer-prone families. This statement is supported by the evidences that BRCA1 and BRCA2 mutations are associated with between 20 to 60% of hereditary breast cancer families, which is less than originally estimated, especially in population-based studies. We have taken the approach that the next BRCA genes will be those that encode for proteins whose functions are linked to important cell regulatory pathways. We have recently found one such candidate BRCA3 protein, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors. Furthermore, our studies have defined BRCC36 as a direct regulator of BRCA1 activation and nuclear foci formation in response to IR in a number of breast cancer cell lines. Our results suggest that down-regulation of BRCC36 expression impairs the DNA repair pathway activated in response to IR and appears to sensitize breast cancer cells to IR-induced apoptosis. Therefore, it is intriguing to speculate that targeting BRCC36 may aid in the treatment of radiation resistant breast tumors,
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA458306
Entities
People
- Xiaowei Chen
Organizations
- Fox Chase Cancer Center