Cooperative assembly of androgen receptor into a nucleoprotein complex that regulates the prostate-specific antigen enhancer

被引：126

作者：

Huang, WB

Shostak, Y

Tarr, P

Sawyers, C

Carey, M

机构：

[1] Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1999年 / 274卷 / 36期

关键词：

D O I：

10.1074/jbc.274.36.25756

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Prostate cancer is characterized by elevated serum levels of prostate-specific antigen (PSA), PSA gene expression is controlled by an androgen-responsive transcriptional enhancer, Our study suggests that formation of a nucleoprotein complex, encompassing 170 base pairs of enhancer DNA, mediates androgen-responsive PSA enhancer activity. The complex is assembled by cooperative binding of androgen receptor to at least four tandem, nonconsensus androgen response elements (AREs). Systematic mutagenesis of the AREs demonstrated that they act synergistically to stimulate androgen receptor-responsive gene expression. We discuss a mechanism whereby a combination of high androgen receptor levels in the prostate and low affinity AREs contribute to the cell type specificity and activity of the enhancer.

引用

收藏

页码：25756 / 25768

页数：13

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