A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element

25 October 2001

journal article
research article
Published by Springer Nature in Oncogene

Vol. 20 (48) , 7110-7114
https://doi.org/10.1038/sj.onc.1204890

Abstract

Transcriptional regulation of the BRCA1 proximal promoter has been suggested to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter reveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 and T-47D cells. This site is shown to be important for the constitutive expression of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP induction. It appears that CREB acts as a constitutive positive element for BRCA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.

Keywords

This publication has 32 references indexed in Scilit:

GA-binding protein α/β is a critical regulator of the BRCA1 promoter
Oncogene, 2000
BRCA1 deficient embryonic stem cells display a decreased homologous recombination frequency and an increased frequency of non-homologous recombination that is corrected by expression of a Brca1 transgene
Oncogene, 1999
A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability
Oncogene, 1998
BRCA1 physically associates with p53 and stimulates its transcriptional activity
Oncogene, 1998
CpG methylation within the 5′ regulatory region of the BRCA1 gene is tumor specific and includes a putative CREB binding site
Oncogene, 1998
Synergism of the ATF/CRE Site and GC Box in the Housekeeping Na,K-ATPase α1 Subunit Gene Is Essential for Constitutive Expression
Biochemical and Biophysical Research Communications, 1997
Location of BRCA1 in Human Breast and Ovarian Cancer Cells
Science, 1996
Distinct transcription start sites generate two forms of BRCA1 mRNA
Human Molecular Genetics, 1995
Cat scratch disease
Australian Veterinary Journal, 1994
Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene
Nature, 1987