Cooperative assembly of androgen receptor into a nucleoprotein complex that regulates the prostate-specific antigen enhancer.
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.
Huang
W
W
Department of Biological Chemistry, Box 1737, UCLA School of Medicine, Los Angeles, California 90095, USA.
Shostak
Y
Y
Tarr
P
P
Sawyers
C
C
Carey
M
M
D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D016296:Mutagenesis; D009698:Nucleoproteins / Q000235:genetics* / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D009698:Nucleoproteins; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen