A zinc finger protein TZF is a novel corepressor of androgen receptor
A zinc finger protein TZF is a novel corepressor of androgen receptor
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DOI：
10.1016/j.bbrc.2005.04.024
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发表时间：
2005-06-17
影响因子：
3.1
通讯作者：
Hagiwara, H
中科院分区：
文献类型：
--
作者：
Ishizuka, M;Kawate, H;Hagiwara, H
类固醇激素通过细胞内核受体调控靶基因的转录活性，这些转录活性通过与辅激活子和辅抑制子的结合来调节。睾丸锌指蛋白（TZF）是一种具有Cys（2）-His（2）锌指结构的核蛋白，是一种新型的雄激素受体（AR）辅阻遏物。融合蛋白与绿色荧光蛋白GFP在细胞核内形成特异性灶，TZF依赖性灶位于剪接因子区室附近。此外，TZF被招募到AR亚核灶后，双氢睾酮的治疗。此外，我们发现TZF结合到AR蛋白的激活功能-1（AF-1）结构域（N-末端反式激活结构域）。TZF在COS-7细胞或LNCaP人前列腺癌细胞中的瞬时过表达以配体依赖的方式导致AR活性降低。此外，转录辅阻遏物N-CoR加性降低AR与TZF的转录活性。这些结果表明TZF可能是一种新的AR辅阻遏物。(c)2005年爱思唯尔公司All rights reserved.
Steroid hormones control the transcriptional activity of target genes mediated by intracellular nuclear receptors, and these transcriptional activities are modulated by the combination with coactivators and corepressors. We found in this study that testicular zinc finger protein (TZF) that was a nuclear protein with a zinc finger motif of the Cys(2)-His(2) type was a novel corepressor of androgen receptor (AR). Fusion protein with green fluorescence protein GFP formed the specific foci in nuclei and TZF-dependent foci were located close to the splicing factor compartment. In addition, TZF was recruited into AR subnuclear foci after the treatment of dihydrotestosterone. Furthermore, we revealed that TZF bound to the activation function-1 (AF-1) domain (N-terminal transactivating domain) of AR protein. Transient over-expression of TZF in COS-7 cells or LNCaP human prostatic cancer cell resulted in decreased AR activity in a ligand-dependent fashion. Moreover, a transcriptional corepressor N-CoR additively decreased the transcriptional activity of AR with TZF. These findings suggest that TZF might be a novel corepressor of AR. (c) 2005 Elsevier Inc. All rights reserved.