Characterization of a Proposed Novel BRCA2 Interaction
Abstract
Mutations in the tumor suppressor breast cancer susceptibility gene 2 (BRCA2), identified in 1994 using linkage analysis and cloned in 1995, are associated with 30-40% of all familial breast cancer cases and, to a lesser extent, with ovarian and pancreatic cancer. In addition, mutations in BRCA2 are strongly linked to hereditary breast cancer in males. Most research has focused on BRCA2 and its involvement in DNA repair due to cellular sensitivity to DNA damaging agents in BRCA2-null mice. Less studied are other possible functions that BRCA2 may perform. Using BRCA2 in a yeast two hybrid assay we identified tristetraprolin (TTP) as a potential interacting protein. TTP was previously shown to be involved in the degradation of TNF-alpha mRNA. This was underscored by TTP-null mice displaying high levels of TNF-alpha and the manifestation of autoimmune-like complications as a result of these elevated levels. We have mapped the area of interaction on BRCA2 using an interaction mating analysis to a stretch of -80 amino acids. We have also demonstrated an in vivo interaction in transfected 293 cells between BRCA2 and TTP. Future studies will attempt to ascertain whether this interaction exerts an influence on the levels of TNF-alpha mRNA.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA417974
Entities
People
- Christopher J. Huggins
Organizations
- Mount Sinai Hospital, Toronto