Trans-activation by thyroid hormone receptors: functional parallels with steroid hormone receptors.
Trans-activation by thyroid hormone receptors: functional parallels with steroid hormone receptors.
复制标题
甲状腺激素受体的反式激活：与类固醇激素受体的功能相似。
DOI：
10.1073/pnas.86.10.3494
复制
发表时间：
1989
影响因子：
11.1
通讯作者：
R. Evans
中科院分区：
文献类型：
--
作者：
C. Thompson;R. Evans
甲状腺激素的作用是通过核受体蛋白介导的，核受体蛋白调节靶细胞中特定基因的转录。我们之前分离了编码两种不同哺乳动物甲状腺激素受体的cDNA，一种来自人胎盘（hTR beta），另一种来自大鼠大脑（rTR alpha），并表明它们的体外翻译产物以天然甲状腺激素受体的特征亲和力结合甲状腺激素。我们现在证明，这两种克隆的受体都以激素依赖性方式激活甲状腺激素响应启动子的转录，其中 rTR α 比 hTR β 引发更大的反应。通过创建嵌合甲状腺激素/糖皮质激素受体来检查甲状腺激素受体的假定功能域，产生具有混合功能特性的受体。这些实验支持甲状腺激素受体由可互换的功能域组成的观点，并表明激素诱导基因调控的机制在类固醇和甲状腺激素受体中是保守的。
The effects of thyroid hormones are mediated through nuclear receptor proteins that modulate the transcription of specific genes in target cells. We previously isolated cDNAs encoding two different mammalian thyroid hormone receptors, one from human placenta (hTR beta) and the other from rat brain (rTR alpha), and showed that their in vitro translation products bind thyroid hormones with the characteritistic affinities of the native thyroid hormone receptor. We now demonstrate that both of the cloned receptors activate transcription from a thyroid hormone-responsive promoter in a hormone-dependent manner, with rTR alpha eliciting a greater response than hTR beta. The putative functional domains of the thyroid hormone receptors were examined by creating chimeric thyroid hormone/glucocorticoid receptors, producing receptors with hybrid functional properties. These experiments support the proposal that the thyroid hormone receptors are composed of interchangeable functional domains, and indicate that the mechanism of hormone-inducible gene regulation has been conserved in steroid and thyroid hormone receptors.