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

Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1020-5. doi: 10.1073/pnas.97.3.1020.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Avian Sarcoma Viruses / genetics
  • BRCA1 Protein / physiology*
  • Binding Sites
  • Bone Neoplasms / pathology
  • Cell Cycle
  • HeLa Cells
  • Humans
  • Kidney
  • Nuclear Proteins / physiology*
  • Osteosarcoma / pathology
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / metabolism
  • Terminal Repeat Sequences
  • Trans-Activators / physiology*
  • Transcription, Genetic*


  • BRCA1 Protein
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators