Negative modulation of androgen receptor transcriptional activity by Daxx

Ding Yen Lin, Hsin I. Fang, Ai Hong Ma, Yen Sung Huang, Yeong Shiau Pu, Guido Jenster, Hsing Jien Kung, Hsiu Ming Shih

研究成果: 雜誌貢獻文章同行評審

93 引文 斯高帕斯(Scopus)

摘要

The transcriptional activity of the androgen receptor (AR) modulated by positive or negative regulators plays a critical role in controlling the growth and survival of prostate cancer cells. Although numerous positive regulators have been identified, negative regulators of AR are less well understood. We report here that Daxx functions as a negative AR coregulator through direct protein-protein interactions. Overexpression of Daxx suppressed AR-mediated promoter activity in COS-1 and LNCaP cells and AR-mediated prostate-specific antigen expression in LNCaP cells. Conversely, downregulation of endogenous Daxx expression by RNA interference enhances androgen-induced prostate-specific antigen expression in LNCaP cells. In vitro and in vivo interaction studies revealed that Daxx binds to both the amino-terminal and the DNA-binding domain of the AR. Daxx proteins interfere with the AR DNA-binding activity both in vitro and in vivo. Moreover, sumoylation of AR at its amino-terminal domain is involved in Daxx interaction and trans-repression. Together, these findings not only provide a novel role of Daxx in controlling AR transactivation activity but also uncover the mechanism underlying sumoylation-dependent transcriptional repression of the AR.
原文英語
頁(從 - 到)10529-10541
頁數13
期刊Molecular and Cellular Biology
24
發行號24
DOIs
出版狀態已發佈 - 十二月 1 2004
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 遺傳學
  • 細胞生物學

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