The research focuses on BRCA1-dependent signaling pathways, whose dysfunction leads to the familial and sporadic breast and ovarian cancer. In particular, this proposal outlines studies on the function of BRCA1 proteins in a transcription factor complex containing p53, which plays a crucial role in cell cycle checkpoint. We have obtained two novel findings: binding of BRCA1 to p53, and stimulation of p53- dependent gene expression by BRCA1. The combined action of BRCA1 and p53 efficiently enhanced p53-dependent gene expression, strongly suggesting a significant role of BRCA1 in cell cycle checkpoint. We propose: i) to further define the function of the BRCA1/p53 complex, and ii) to investigate the mechanisms underlying p53-dependent gene expression.
Specific Aims are i) to investigate the regulation of BRCA-mediated gene expression, 2) to characterize the minimal binding region of BRCA1 and p53, and 3) to investigate the role of BRCA1 phosphorylation to stimulate p53-dependent gene expression.
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