BCCIP Functions through p53 to Regulate the Expression of p21Waf1/Cip1

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Abstract
The BCCIP protein is a BRCA2 and CDKN1A (p21Waf1/Cip1) Interacting Protein, which binds to a highly conserved domain of BRCA2, and a C-terminal domain of the CDK-inhibitor p21. We have previously reported that overexpression of BCCIP increases p21 mRNA and protein levels, and inhibits G1 to S progression. In this report, we show that a partial shutdown of BCCIP expression by RNA interference reduces p21 levels and impairs G1/S checkpoint activation in response to ionizing radiation in HT1080 cells. We further show that the regulation of p21 expression by BCCIP is dependent on p53, and BCCIP regulates p53 transcription activity. These data provide a new mechanism by which BCCIP regulates p21 functions.

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