THE TAU-4 ACTIVATION DOMAIN OF THE THYROID-HORMONE RECEPTOR IS REQUIRED FOR RELEASE OF A PUTATIVE COREPRESSOR(S) NECESSARY FOR TRANSCRIPTIONAL SILENCING
THE TAU-4 ACTIVATION DOMAIN OF THE THYROID-HORMONE RECEPTOR IS REQUIRED FOR RELEASE OF A PUTATIVE COREPRESSOR(S) NECESSARY FOR TRANSCRIPTIONAL SILENCING
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DOI：
10.1128/mcb.15.1.76
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发表时间：
1995-01-01
影响因子：
5.3
通讯作者：
OMALLEY, BW
中科院分区：
文献类型：
--
作者：
BANIAHMAD, A;LENG, XH;OMALLEY, BW
核激素受体的C末端是一个包含多种功能的复杂结构。我们感兴趣的是甲状腺激素将其受体从转录沉默子转化为转录激活子的机制。这两种调节功能都位于该受体超家族成员的配体结合结构域中。在这项研究中，我们已经确定和特点的人甲状腺激素受体（TRP）的配体结合域内的几个功能域赋予转录激活。有趣的是，这些结构域位于激素结合位点附近。一个激活结构域，命名为tau 4，长度仅为17个氨基酸，位于TR的C末端。tau 4的6个氨基酸的缺失导致仍然可以结合激素但充当组成性沉默物的受体，这表明tau 4是转录激活和沉默功能的缓解所需的。此外，我们进行了体内竞争实验，其结果表明，在没有tau 4或激素的情况下，TR被辅阻遏蛋白结合，激素的一个作用是从受体释放辅阻遏物。我们提出了一个一般的模型，其中激素的作用是诱导受体的构象变化，随后影响tau 4的作用，导致沉默和转录激活的救济。
The C terminus of nuclear hormone receptors is a complex structure that contains multiple functions. We are interested in the mechanism by which thyroid hormone converts its receptor from a transcriptional silencer to an activator of transcription. Both regulatory functions are localized in the ligand binding domain of this receptor superfamily member. In this study, we have identified and characterized several functional domains within the ligand binding domain of the human thyroid hormone receptor (TRP) conferring transactivation. Interestingly, these domains are localized adjacent to hormone binding sites. One activation domain, designated tau 4, is only 17 amino acids in length and is localized at the extreme C terminus of TR. Deletion of six amino acids of tau 4 resulted in a receptor that could still bind hormone but acted as a constitutive silencer, indicating that tau 4 is required for both transactivation and relief of the silencing functions. In addition, we performed in vivo competition experiments, the results of which suggest that in the absence of tau 4 or hormone, TR is bound by a corepressor protein(s) and that one role of hormone is to release corepressor from the receptor. We propose a general model in which the role of hormone is to induce a conformational change in the receptor that subsequently affects the action of tau 4, leading to both relief of silencing and transcriptional activation.