A novel domain of BRCA1 interacts with p53 in breast cancer cells

Cancer Lett. 2008 Sep 8;268(1):137-45. doi: 10.1016/j.canlet.2008.03.061. Epub 2008 May 22.

Abstract

The interactions between BRCA1 and p53 are relevant for understanding hereditary breast and ovarian cancer. Although in vitro studies reported that BRCA1 (amino acids 224-500) and the second BRCT domain of the BRCA1 C-terminus may interact with p53, quantitative biophysical measurements indicate that these regions of BRCA1 do not bind efficiently to p53. Here we show that BRCA1 interacts with p53 in vivo in breast cancer cells, through another BRCA1 domain (amino acids 772-1292). Expression of a truncated BRCA1 (amino acids 772-1292) stimulated p53 DNA-binding and transcription activities and apoptosis, recapitulating some effects of DNA damage. These results suggest that a novel domain of BRCA1 may interact with p53 in breast cancer cells.

Publication types

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

MeSH terms

  • Apoptosis
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / metabolism*
  • Breast Neoplasms / metabolism*
  • Female
  • Humans
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary*
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • BRCA1 Protein
  • Tumor Suppressor Protein p53