Department of Urology, University of Pittsburgh, Pittsburgh, PA, United States.
J Steroid Biochem Mol Biol. 2014 Jan;139:16-24. doi: 10.1016/j.jsbmb.2013.09.013. Epub 2013 Oct 4.
Nucleocytoplasmic trafficking of the androgen receptor (AR) represents an essential step in androgen action. To determine whether the amino-terminal domain (NTD) contains potential nuclear import and/or export signals, deletion mutants of the NTD tagged with green fluorescent protein (GFP) were generated and tested for their intracellular localization in both AR-negative and AR-positive cell lines. Subcellular localization analysis suggested a role of the NTD in regulating AR subcellular localization and revealed that the region of a.a. 50-250 of the NTD of AR (AR(50-250)) could promote cytoplasmic localization. Leptomycin B inhibited the activity of AR(50-250), suggesting that AR(50-250) export is mediated through exportin 1, either directly or indirectly. These observations argue for an important role of the NTD in regulating AR nucleocytoplasmic trafficking and will facilitate further investigation of interactions among different signals in regulating AR nucleocytoplasmic trafficking, which may lead to new approaches to inhibit AR nuclear localization.
核质转运的雄激素受体（AR）代表了雄激素作用的一个重要步骤。为了确定氨基末端结构域（NTD）是否包含潜在的核输入和/或输出信号，用绿色荧光蛋白（GFP）标记的 NTD 缺失突变体被生成，并在 AR 阴性和 AR 阳性细胞系中测试其细胞内定位。亚细胞定位分析表明 NTD 在调节 AR 亚细胞定位中起作用，并揭示了 AR 的 NTD 区域的 a.a.50-250（AR（50-250））可以促进细胞质定位。莱普霉素 B 抑制了 AR（50-250）的活性，表明 AR（50-250）的输出是通过 exportin 1 介导的，无论是直接还是间接。这些观察结果表明 NTD 在调节 AR 核质转运中起着重要作用，并将有助于进一步研究不同信号在调节 AR 核质转运中的相互作用，这可能导致抑制 AR 核定位的新方法。
