BRCA1, a breast and ovarian cancer susceptibility gene, encodes a 220-kDa p
rotein 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 w
ith RNA polymerase holoenzyme. Using the yeast two-hybrid system, we identi
fied an interaction between the BRCA1 RING finger and ATF1, a member of the
cAMP response element-binding protein/activating transcription factor (CRE
B/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 al
so 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 ATF
1 target genes, some of which are involved in the transcriptional response
to DNA damage.