A novel domain of BRCA1 interacts with p53 in breast cancer cells.
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.
Buck
Martina
M
Department of Medicine, Veterans Healthcare Medical Center, San Diego, CA 92161, USA. mbuck@ucsd.edu
D017209:Apoptosis; D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019313:BRCA1 Protein; D016159:Tumor Suppressor Protein p53