GA-binding protein alpha/beta is a critical regulator of the BRCA1 promoter.
Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced effect in T47D cells. The main transcription factor interacting with this site was identified as GABPalpha/beta, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPalpha and beta1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPalpha/beta is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.
Atlas
E
E
Cancer Research Laboratories, Department of Biochemistry, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Stramwasser
M
M
Whiskin
K
K
Mueller
C R
CR
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; C495656:Gabpa protein, mouse; C495658:Gabpb1 protein, mouse; D014157:Transcription Factors