BRCA1 SPLICE VARIANTS BRCA1A AND BRCA1B ASSOCIATE WITH CBP COACTIVATOR

The tumor suppressor gene BRCA1, is a nuclear phosphoprotein which ass ociates with RNA polymerase II holoenzyme. CBP is a component of the h oloenzyme. Previously, we have characterized two new BRCA1 splice vari ants BRCA1a/p110 and BRCA1b/p100. In the present study, the carboxy-te rminal domain of transcription factor CBP interacts both in vivo and i n vitro with full length BRCA1a and BRCA1b proteins as demonstrated by mammalian two-hybrid assays, co-immunoprecipitation/Western blot stud ies, GST binding assays and histone acetyl transferase (HAT) assays of BRCA1 immunoprecipitates from human breast cancer cells. Our results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP associated HAT/FAT (transcription factor a cetyltransferase) activity for acetylation of either themselves or gen eral transcription factors or both to specific promoters resulting in transcriptional activation.