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1 October 2002 Activating Signal Cointegrator 1 Is Highly Expressed in Murine Testicular Leydig Cells and Enhances the Ligand-Dependent Transactivation of Androgen Receptor
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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.

Yong Soo Lee, Hyun-Jin Kim, Hyun Ju Lee, Jae Woon Lee, Sang-Young Chun, Sun-Kun Ko, and Keesook Lee "Activating Signal Cointegrator 1 Is Highly Expressed in Murine Testicular Leydig Cells and Enhances the Ligand-Dependent Transactivation of Androgen Receptor," Biology of Reproduction 67(5), 1580-1587, (1 October 2002). https://doi.org/10.1095/biolreprod.102.006155
Received: 1 April 2002; Accepted: 1 June 2002; Published: 1 October 2002
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