BRCA1近端启动子中的一个CREB位点作为一个组成型转录元件发挥作用。

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

作者信息

Atlas E, Stramwasser M, Mueller C R

机构信息

Cancer Research Laboratories, Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.

出版信息

Oncogene. 2001 Oct 25;20(48):7110-4. doi: 10.1038/sj.onc.1204890.

DOI:10.1038/sj.onc.1204890

PMID:11704836

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.

摘要

BRCA1近端启动子的转录调控被认为在散发性乳腺癌中观察到的BRCA1表达降低中起作用。对近端启动子序列的计算机分析揭示了一个潜在的CREB位点的存在。我们已经确定CREB/ATF-1是与MCF-7和T-47D细胞核提取物中该位点相互作用的因子。该位点对于这些细胞以及Hep G2细胞中启动子的组成型表达很重要。尽管存在该位点，但BRCA1启动子对cAMP诱导无反应。似乎CREB作为BRCA1表达的组成型正性元件，任何使CREB功能失活的机制都会对BRCA1表达产生显著影响。