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

BRCA1 is a breast and ovarian cancer-specific tumor suppressor, with proper ties of a transcription factor involved in DNA repair. We previously have s hown 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 t he adenovirus E1A oncoprotein, We show a physical association of BRCA1 with the transcriptional coactivators/acetyltransferases p300 and CBP, Endogeno us as well as overexpressed BRCA1 and p300 were found to associate in a pho sphorylation-independent manner. BRCA1 interacts with the cAMP response ele ment binding protein (CREB) domain of p300/CBP via both its amino and carbo xyl termini. Finally, full-length BRCA1 is shown to transcriptionally activ ate the Rous sarcoma virus-long terminal repeat promoter, which was further stimulated by p300, Immunocolocalization analyses suggest that BRCA1 and p 300 associate in a cell cycle-dependent manner. Our results support a role for BRCA1 in transcription.