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 Lee, Sang Young Chun, Sun Kun Ko, Keesook Lee

Research output: Contribution to journalArticle

22 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Leydig Cells
Androgen Receptors
Transcriptional Activation
Testis
Ligands
Reporter Genes
Messenger RNA
Nuclear Receptor Coactivators
Zinc Fingers
Spermatogenesis
Glutathione Transferase
Androgens
Open Reading Frames
In Situ Hybridization
Transfection
Organism Cloning
Yeasts

Keywords

  • Androgen receptor
  • Leydig cells
  • Testis

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor. / Lee, Yong Soo; Kim, Hyun Jin; Lee, Hyun Ju; Lee, Jae; Chun, Sang Young; Ko, Sun Kun; Lee, Keesook.

In: Biology of Reproduction, Vol. 67, No. 5, 01.11.2002, p. 1580-1587.

Research output: Contribution to journalArticle

Lee, Yong Soo ; Kim, Hyun Jin ; Lee, Hyun Ju ; Lee, Jae ; Chun, Sang Young ; Ko, Sun Kun ; Lee, Keesook. / Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor. In: Biology of Reproduction. 2002 ; Vol. 67, No. 5. pp. 1580-1587.
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