BRCA1 Mediated Ubiquitination: Identification of Targets for Destruction
Abstract
I have made considerable progress on the research project that I outlined in the pre-doctoral DOD breast cancer research fellowship proposal. The proposal aimed to determine targets for the ubiquitin ligase activity of BRCA1. BRCA1 (Breast Cancer susceptibility gene 1) is an important tumor suppressor that protects mammary cells from malignant transformation. Recently BRCA1 has been found to have an enzymatic function as an ubiquitin ligase. Ubiquitin ligases tag other proteins with a small peptide, ubiquitin, and these tagged proteins then signal for downstream events such as protein degradation or DNA repair. Determination of the targets for ubiquitination by BRCA1 will lead to a better understanding of how this protein performs its tumor suppressor function. The specific aims for this project are as follows: 1. Identify targets for ubiquitination by BRCA1 A. Biochemical experiments: use of purified BRCA1-containing complexes and ubiquitin activating and conjugating enzymes for in vitro reactions to determine which proteins are ubiquitinated by BRCA1. B. Biological experiments: use of HCC1937 cells, which contain a truncated form of BRCA1 to test the function of the carboxy-terminus in the regulation of ubiquitination. 2. Reconstitution of BRCA1 ubiquitination in a pathway in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA447250
Entities
People
- Jeffrey Parvin
- Lea M Starita
Organizations
- Brigham and Women's Hospital