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BRCA1 regulates p53-dependent gene expression.

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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Ouchi T,Monteiro AN,August A,Aaronson SA,Hanafusa H

doi

10.1073/pnas.95.5.2302

subject

Has Abstract

pub_date

1998-03-03 00:00:00

pages

2302-6

issue

5

eissn

0027-8424

issn

1091-6490

journal_volume

95

pub_type

杂志文章

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