BRCA1 splice variants BRCA1a and BRCA1b associate with CBP co-activator.
The tumor suppressor gene BRCA1, is a nuclear phosphoprotein which associates with RNA polymerase II holoenzyme. CBP is a component of the holoenzyme. Previously, we have characterized two new BRCA1 splice variants BRCA1a/p110 and BRCA1b/p100. In the present study, the carboxy-terminal domain of transcription factor CBP interacts both in vivo and in vitro with full length BRCA1a and BRCA1b proteins as demonstrated by mammalian two- hybrid assays, co-immunoprecipitation/western blot studies, 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 acetyl-transferase) activity for acetylation of either themselves or general transcription factors or both to specific promoters resulting in transcriptional activation.
Cui
J Q
JQ
Division of Cancer Genetics, Department of Human Genetics, Allegheny University of the Health Sciences, M.S. 481, New College Building, Broad and Vine Streets, Philadelphia, PA 19102, USA.
Shao
N
N
Chai
Y
Y
Wang
H
H
Reddy
E S
ES
Rao
V N
VN
D000123:Acetyltransferases / Q000378:metabolism; D017398:Alternative Splicing; D019313:BRCA1 Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050882:CREB-Binding Protein; D005260:Female; D019398:Genes, BRCA1; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D011233:Precipitin Tests; D015534:Trans-Activators; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D005982:Glutathione Transferase