CBP/p300 interact with and function as transcriptional coactivators of BRCA1.
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.
Mesh Terms:
Avian Sarcoma Viruses, BRCA1 Protein, Binding Sites, Bone Neoplasms, Cell Cycle, Hela Cells, Humans, Kidney, Nuclear Proteins, Osteosarcoma, Phosphorylation, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins, Terminal Repeat Sequences, Trans-Activators, Transcription, Genetic
Avian Sarcoma Viruses, BRCA1 Protein, Binding Sites, Bone Neoplasms, Cell Cycle, Hela Cells, Humans, Kidney, Nuclear Proteins, Osteosarcoma, Phosphorylation, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins, Terminal Repeat Sequences, Trans-Activators, Transcription, Genetic
Proc. Natl. Acad. Sci. U.S.A.
Date: Feb. 01, 2000
PubMed ID: 10655477
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