Tob proteins suppress steroid hormone receptor-mediated transcriptional activation
Tob proteins suppress steroid hormone receptor-mediated transcriptional activation
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DOI：
10.1016/j.mce.2004.10.009
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发表时间：
2005-01-31
影响因子：
4.1
通讯作者：
Takayanagi, R
中科院分区：
文献类型：
--
作者：
Kawate, H;Wu, Y;Takayanagi, R
虽然性类固醇激素对骨代谢有显著影响，但其作用的分子机制尚未完全阐明。我们研究了类固醇激素受体和Tob之间的功能关系，Tob是一个抗伸展蛋白家族的成员，也是成骨细胞增殖和分化的负调控因子。使用携带激素反应元件的启动子的荧光素酶分析显示，在MC3T3-E1成骨细胞中，Tob1和Tob2蛋白而不是PC3抑制了类固醇激素受体依赖的转录激活。带有LxxLL基序氨基酸替换的突变ToB蛋白也显示出与野生型相同程度的转录激活抑制。通过在激光共聚焦显微镜下观察绿色荧光蛋白标记的雄激素受体(AR)，我们发现Tob1抑制了双氢睾酮结合AR的核焦点的形成。这些结果表明，Tob家族蛋白可能负向调节性类固醇激素在骨形成中的作用。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Although sex steroid hormones have significant effects on bone metabolism, the molecular mechanisms of these actions have not been fully elucidated yet. We examined the functional relationship between steroid hormone receptors and Tob, a member of an anti-prolifelative protein family and a negative regulator of osteoblast proliferation and differentiation. Luciferase assay using promoters carrying hormone-responsive elements revealed that both Tob1 and Tob2 proteins but not PC3 suppressed steroid hormone receptor-dependent transcriptional activation in MC3T3-E1 osteoblastic cells. Mutated Tob proteins carrying amino acid substitutions at an LXXLL motif also showed the same degree of inhibition of the transcriptional activation as the wild type. By observation of androgen receptor (AR)-tagged with green fluorescent protein under a confocal laser scanning microscope, we found that Tob1 inhibits the nuclear foci formation of dihydrotestosterone-bound AR. These results indicate that Tob family proteins may negatively regulate sex steroid hormone action in bone formation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.