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
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.
Biology of Reproduction
https://doi.org/10.1095/biolreprod.102.006155
Leydig Cells
Androgen Receptors
Transcriptional Activation
Reporter Genes
Nuclear Receptor Coactivators
Zinc Fingers
Androgen receptor
Lee, Y. S., Kim, H. J., Lee, H. J., Lee, J., Chun, S. Y., Ko, S. K., & Lee, K. (2002). 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. https://doi.org/10.1095/biolreprod.102.006155
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.
Lee, YS, Kim, HJ, Lee, HJ, Lee, J, Chun, SY, Ko, SK & Lee, K 2002, 'Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor', Biology of Reproduction, vol. 67, no. 5, pp. 1580-1587. https://doi.org/10.1095/biolreprod.102.006155
Lee YS, Kim HJ, Lee HJ, Lee J, Chun SY, Ko SK et al. Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor. Biology of Reproduction. 2002 Nov 1;67(5):1580-1587. https://doi.org/10.1095/biolreprod.102.006155
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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title = "Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor",
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.",
keywords = "Androgen receptor, Leydig cells, Testis",
author = "Lee, {Yong Soo} and Kim, {Hyun Jin} and Lee, {Hyun Ju} and Jae Lee and Chun, {Sang Young} and Ko, {Sun Kun} and Keesook Lee",
doi = "10.1095/biolreprod.102.006155",
journal = "Biology of Reproduction",
publisher = "Society for the Study of Reproduction",
T1 - Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor
AU - Lee, Yong Soo
AU - Kim, Hyun Jin
AU - Lee, Hyun Ju
AU - Lee, Jae
AU - Chun, Sang Young
AU - Ko, Sun Kun
AU - Lee, Keesook
N2 - 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.
AB - 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.
KW - Androgen receptor
KW - Leydig cells
U2 - 10.1095/biolreprod.102.006155
DO - 10.1095/biolreprod.102.006155
JO - Biology of Reproduction
JF - Biology of Reproduction
10.1095/biolreprod.102.006155