Structural determinants of the BRCA1 : estrogen receptor interaction.

Previously, we showed that the BRCA1 protein interacts directly and functionally with estrogen receptor-alpha (ER-alpha), resulting in the inhibition of estradiol (E2)-stimulated ER-alpha transcriptional activity. The interaction sites were mapped to the N-terminus of BRCA1 (within amino acids (aa) 1-302) and the ligand-binding domain/activation function-2 (LBD/AF-2) region (within aa 282-420) of ER-alpha. In this study, we have further characterized the structure/function relationship for the BRCA1 : ER-alpha interaction.

Role of BRCA1 in heat shock response.

The heat shock response is an evolutionarily conserved response to heat and other stresses that promotes the maintenance of key metabolic functions and cell survival. We report that exposure of human prostate (DU-145) and breast (MCF-7) cancer cells to heat (42 degrees C) caused a rapid disappearance of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at approximately 1 h after the onset of heating and slightly lagging behind the increase in heat shock protein 70 (HSP70) levels. The heat-induced loss of BRCA1 occurred at the protein level, since: (1) BRCA1 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells that expressed exogenous wild-type BRCA1 (wtBRCA1).

p300 Modulates the BRCA1 inhibition of estrogen receptor activity.

We previously reported that expression of the breast cancer susceptibility gene BRCA1 strongly inhibits the transcriptional activity of the estrogen receptor (ER-alpha) in human breast and prostate cancer cell lines but only weakly inhibits ER-alpha activity in cervical cancer cells (S. Fan et al., Science (Wash.