Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor
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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DOI：
10.1095/biolreprod.102.006155
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发表时间：
2002-11-01
影响因子：
3.6
通讯作者：
Lee, K
中科院分区：
文献类型：
--
作者：
Lee, YS;Kim, HJ;Lee, K
最近有报道称激活信号协整合子 1 (ASC-1) 是某些核受体的共激活子。在本研究中，我们分析了小鼠睾丸中 ASC-1 的表达，并研究了其调节雄激素受体 (AR) 转录活性的能力。我们发现，尽管 ASC-1 mRNA 在小鼠组织中以低水平普遍表达，但一些睾丸特异性 mRNA 在成年睾丸中表达。一种睾丸特异性变体的克隆表明，ASC-1 普遍存在的转录本和睾丸特异性转录本至少共享相同的开放阅读框。睾丸特异性 ASC-1 mRNA 的表达受到发育调节，其表达的开始与精子发生的开始一致。小鼠睾丸与 ASC-1 反义探针的原位杂交表明，ASC-1 在表达 AR 的间质 Leydig 细胞中占主导地位。此外，酵母双杂交测试和谷胱甘肽S-转移酶下拉测定表明，ASC-1直接与AR相关，并且AR的铰链结构域和ASC-1的假定锌指基序是它们相互作用的主要决定因素。通过表达 ASC-1 与 AR 和雄激素响应报告基因组合进行的瞬时转染测定表明，ASC-1 适度改变报告基因的诱导。总而言之，这些结果表明 ASC-1 可能作为 AR 核心调节器发挥作用，并在睾丸功能中发挥作用。
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.