CBP/p300 interact with and function as transcriptional coactivators of BRCA1

被引:177
作者
Pao, GM
Janknecht, R
Ruffner, H
Hunter, T
Verma, IM
机构
[1] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Mol Biol & Virol Lab, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
[4] Mayo Clin & Mayo Fdn, Dept Biochem, Rochester, MN 55905 USA
关键词
D O I
10.1073/pnas.97.3.1020
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1020 / 1025
页数:6
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