National Academy of Sciences, Proceedings of the National Academy of Sciences, 5(95), p. 2302-2306, 1998
Full text: Download
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.