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.
Pao
G M
GM
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Janknecht
R
R
Ruffner
H
H
Hunter
T
T
Verma
I M
IM
D001358:Avian Sarcoma Viruses / Q000235:genetics; D019313:BRCA1 Protein / Q000502:physiology*; D001665:Binding Sites; D001859:Bone Neoplasms / Q000473:pathology; D002453:Cell Cycle; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D009687:Nuclear Proteins / Q000502:physiology*; D012516:Osteosarcoma / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020079:Terminal Repeat Sequences; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D019313:BRCA1 Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators