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Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2302-6.

BRCA1 regulates p53-dependent gene expression.

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  • 1Laboratory of Molecular Oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

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.

PMID:
9482880
[PubMed - indexed for MEDLINE]
PMCID:
PMC19327
Free PMC Article

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