BRCA2 associates with acetyltransferase activity when bound to P/CAF.
Predisposition to hereditary breast cancer has been attributed in part to inherited mutations in the BRCA2 gene. The large protein it encodes is still poorly characterized with respect to functions. We have previously shown that BRCA2 has transcriptional activation potential conferred by its amino-terminal third exon. Here, we show that BRCA2 interacts with a transcriptional co-activator protein, P/CAF, which possesses histone acetyltransferase activity. The interaction with P/CAF is demonstrated in vitro as well as in vivo and is shown to be mediated by residues 290-453 of BRCA2. Consistent with the binding to an acetyltransferase, BRCA2 is shown to associate with acetyltransferase activity in nuclear extracts. Contrary to a recent report, we find no evidence in support of an intrinsic HAT activity in BRCA2 amino-terminus. Our results further substantiate the notion that BRCA2 has transcriptional activation function and suggest that one mechanism by which BRCA2 regulates transcription may be through the recruitment of histone-modifying activity of the P/CAF co-activator.
Fuks
F
F
Wellcome/CRC Institute and Department of Pathology, Cambridge University, UK.
Milner
J
J
Kouzarides
T
T
D000123:Acetyltransferases / Q000378:metabolism*; D024682:BRCA2 Protein; D002467:Cell Nucleus / Q000378:metabolism; D005091:Exons; D051548:Histone Acetyltransferases; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases