BRCA1 physically and functionally interacts with ATF1.
BRCA1, a breast and ovarian cancer susceptibility gene, encodes a 220-kDa protein whose precise biochemical function remains unclear. BRCA1 contains an N-terminal RING finger that mediates protein-protein interaction. The C-terminal domain of BRCA1 (BRCT) can activate transcription and interacts with RNA polymerase holoenzyme. Using the yeast two-hybrid system, we identified an interaction between the BRCA1 RING finger and ATF1, a member of the cAMP response element-binding protein/activating transcription factor (CREB/ATF) family. We demonstrate that BRCA1 and ATF1 can physically associate in vitro, in yeast, and in human cells. BRCA1 stimulated transcription from a cAMP response element reporter gene in transient transfections. BRCA1 also stimulated transcription from a natural promoter, that of tumor necrosis factor-alpha, in a manner dependent on the integrity of the cAMP response element. These results implicate BRCA1 in transcriptional activation of ATF1 target genes, some of which are involved in the transcriptional response to DNA damage.
Houvras
Y
Y
Derald H. Ruttenberg Cancer Center and the Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Benezra
M
M
Zhang
H
H
Manfredi
J J
JJ
Weber
B L
BL
Licht
J D
JD
D051697:Activating Transcription Factor 1; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D020798:Two-Hybrid System Techniques
D051697:Activating Transcription Factor 1; D019313:BRCA1 Protein; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha