Activation Function-1 Domain of Androgen Receptor Contributes to the Interaction between Subnuclear Splicing Factor Compartment and Nuclear Receptor Compartment
Activation Function-1 Domain of Androgen Receptor Contributes to the Interaction between Subnuclear Splicing Factor Compartment and Nuclear Receptor Compartment
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DOI：
10.1074/jbc.m203811200
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发表时间：
2002-08
期刊：
影响因子：
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通讯作者：
Yue Zhao;K. Goto;M. Saitoh;T. Yanase;M. Nomura;T. Okabe;R. Takayanagi;H. Nawata
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文献类型：
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作者：
Yue Zhao;K. Goto;M. Saitoh;T. Yanase;M. Nomura;T. Okabe;R. Takayanagi;H. Nawata
在雄激素受体（AR）中，其大部分的转激活活性是通过激活功能-1 （AF-1）介导的。通过酵母双杂交实验，我们分离到了一个编码AR-AF-1结合蛋白的cDNA序列。该蛋白被命名为ANT-1 (AR n-末端结构域反激活蛋白-1)，增强AR或糖皮质激素受体不依赖配体的AF-1自主反激活功能，但不增强雌激素受体α的反激活功能。相反，ANT-1不增强任何配体依赖性AF-2活性。此外，在体内和体外证实了AR-AF-1和ANT-1之间不依赖配体的相互作用。ANT-1序列与U5小核核糖核蛋白颗粒（酵母剪接因子Prp6p的人类同源物，参与剪接体）的蛋白序列相同。在弥漫性网状分布的背景下，ANT-1被划分为20-40个粗剪接因子区室斑点。AR仅在弥漫性分布的区域与ANT-1共域，而ANT-1斑点在空间上与AR室不同，但被AR室包围。活性基因转录已被证明与剪接因子室外围的前mrna加工同时偶联。因此，由ANT-1介导的两个空间上不同的亚核区室之间的分子相互作用可能将AR招募到转录-剪接-偶联机制中。
In the androgen receptor (AR), most of its transactivation activity is mediated via the activation function-1 (AF-1). By employing yeast two-hybrid assay, we isolated a cDNA sequence encoding a protein binding to AR-AF-1. This protein, named ANT-1 (AR N-terminal domain transactivating protein-1), enhanced the ligand-independent autonomous AF-1 transactivation function of AR or glucocorticoid receptor but did not enhance that of estrogen receptor α. In contrast, the ANT-1 did not enhance any ligand-dependent AF-2 activities. Furthermore, the ligand-independent interaction between AR-AF-1 and ANT-1 was confirmedin vivo and in vitro. The ANT-1 sequence was identical to that of a protein that binds to U5 small nuclear ribonucleoprotein particle, a human homologue of yeast splicing factor Prp6p, involved in spliceosome. ANT-1 was compartmentalized into 20–40 coarse splicing factor compartment speckles against the background of the diffuse reticular distribution. AR colocalized with ANT-1 only in the diffusely distributed area, whereas the ANT-1 speckles were spatially distinct from but surrounded by the AR compartments. The active gene transcription has been shown to couple simultaneously with pre-mRNA processing at the periphery of the splicing factor compartment. The molecular interaction between two spatially distinct subnuclear compartments mediated by ANT-1 may therefore recruit AR into the transcription-splicing-coupling machinery.