Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor

Yong Soo Lee, Hyun Jin Kim, Hyun Ju Lee, Jae Woon Lee, Sang Young Chun, Sun Kun Ko, Keesook Lee

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Activating signal cointegrator 1 (ASC-1) has been recently reported as a coactivator of some nuclear receptors. In the present study, we have analyzed the expression of ASC-1 in the mouse testis and investigated its capacity to modulate the transcriptional activity of androgen receptor (AR). We found that although ASC-1 mRNA was ubiquitously expressed at a low level in mouse tissues, a couple of testis-specific mRNAs were expressed in the adult testis. Cloning of one testis-specific variant revealed that the ubiquitous and testis-specific transcripts of ASC-1 share at least the same open reading frame. The expression of the testis-specific ASC-1 mRNAs was developmentally regulated, and the onset of their expression coincided with the initiation of spermatogenesis. In situ hybridization of mouse testis with ASC-1 antisense probe demonstrated predominant expression of ASC-1 in the interstitial Leydig cells that express AR. Moreover, yeast two-hybrid tests and glutathione S-transferase pull-down assays revealed that ASC-1 associates directly with AR and that the hinge domain of AR and a putative zinc-finger motif of ASC-1 are major determinants for their interaction. Transient transfection assays performed by expressing ASC-1 in combination with AR and an androgen-responsive reporter gene showed that ASC-1 moderately alters the induction of the reporter gene. Taken together, these results suggest that ASC-1 may function as an AR coregulator and have a role in testicular functions.

Original languageEnglish (US)
Pages (from-to)1580-1587
Number of pages8
JournalBiology of reproduction
Volume67
Issue number5
DOIs
StatePublished - Nov 1 2002

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Keywords

  • Androgen receptor
  • Leydig cells
  • Testis

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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