Abstract
BRCA1 is a breast and ovarian cancer-specific tumor suppressor, with properties of a transcription factor involved in DNA repair. We previously have shown the transactivation of heterologous promoters by the carboxyl terminus of BRCA1. We now describe that BRCA1-mediated transactivation is enhanced by p300/CBP (CREB binding protein) and that this effect was suppressed by the adenovirus E1A oncoprotein. We show a physical association of BRCA1 with the transcriptional coactivators/acetyltransferases p300 and CBP. Endogenous as well as overexpressed BRCA1 and p300 were found to associate in a phosphorylation-independent manner. BRCA1 interacts with the cAMP response element binding protein (CREB) domain of p300/CBP via both its amino and carboxyl termini. Finally, full-length BRCA1 is shown to transcriptionally activate the Rous sarcoma virus-long terminal repeat promoter, which was further stimulated by p300. Immunocolocalization analyses suggest that BRCA1 and p300 associate in a cell cycle-dependent manner. Our results support a role for BRCA1 in transcription.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:38 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 5:51 p.m.) |
Indexed | 1 month, 4 weeks ago (July 1, 2025, 9:48 a.m.) |
Issued | 25 years, 7 months ago (Feb. 1, 2000) |
Published | 25 years, 7 months ago (Feb. 1, 2000) |
Published Online | 25 years, 7 months ago (Feb. 1, 2000) |
Published Print | 25 years, 7 months ago (Feb. 1, 2000) |
@article{Pao_2000, title={CBP/p300 interact with and function as transcriptional coactivators of BRCA1}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.97.3.1020}, DOI={10.1073/pnas.97.3.1020}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Pao, Gerald M. and Janknecht, Ralf and Ruffner, Heinz and Hunter, Tony and Verma, Inder M.}, year={2000}, month=feb, pages={1020–1025} }