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BRCA1 regulates p53-dependent gene expression.

T Ouchi·A N Monteiro·A August·S A Aaronson·H Hanafusa
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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.

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AnimalsBRCA1 ProteinBreastCell LineEpithelial CellsFemaleGene Expression RegulationGenes, BRCA1Genes, ReporterGlutathione TransferaseHumansKidney NeoplasmsLuciferasesMicePolymerase Chain ReactionPromoter Regions, GeneticRecombinant Fusion ProteinsTransfectionTumor Cells, CulturedTumor Suppressor Protein p53Journal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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T Ouchi, A N Monteiro, A August, S A Aaronson, H Hanafusa. 1998-03-03. BRCA1 regulates p53-dependent gene expression.. https://doi.org/10.1073/pnas.95.5.2302

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