期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：5
页码：2302-2306
DOI：10.1073/pnas.95.5.2302
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
