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BRCA1 regulates p53-dependent gene expression

By Toru Ouchi, Alvaro N. A. Monteiro, Avery August, Stuart A. Aaronson and Hidesaburo Hanafusa

Abstract

Mutations in BRCA1 are present in 45% of families that segregate with susceptibility for breast cancer and in 80–90% of families with both breast and ovarian cancer. Here we report that BRCA1 stimulates artificial and genomic promoter constructs containing p53-responsive elements. This activity of BRCA1 depends on the presence of wild-type p53, which was shown by using mouse fibroblasts expressing temperature-sensitive forms of p53, or p53(+/+) and p53(−/−) fibroblasts obtained from p53 knockout mice. Furthermore, mutant forms of BRCA1 lacking the C-terminal second BRCA1 C-terminal (BRCT) domain showed reduced p53-mediated transcriptional activation. Finally, we found that BRCA1 coimmunoprecipitates with p53, in vitro and in vivo. These findings suggest a function of BRCA1 as a p53 coactivator

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 1998
OAI identifier: oai:pubmedcentral.nih.gov:19327
Provided by: PubMed Central
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