Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity
Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity
复制标题
甲状腺激素受体的双重调节作用可以控制视黄酸受体的活性
作者：
G. Graupner;K. Wills;M. Tzukerman;Xiao;M. Pfahl
甲状腺激素 (T3) 和视黄酸都发出发育、分化和形态发生中重要步骤的信号。这些配体的特异性核受体最近已被克隆1-8。之前我们已经注意到 ε-视黄酸受体（RAR-ε，也称为 RAR-β）、甲状腺激素受体和雌激素受体的 DNA 结合域之间存在密切同源性2,9。我们现在发现 RAR-ε 在诱导两种不同的甲状腺激素反应元件 (TRE) 转录方面非常有效。然而，在缺乏配体的情况下，由 TRE 配体激活的 RAR-ε 诱导的转录可以被甲状腺激素受体抑制。相反，在其配体存在的情况下，甲状腺激素受体将激活 TRE 的转录，无论是否存在未结合的 RAR。杂合受体的使用表明，RAR 的 DNA 结合结构域是甲状腺激素受体抑制的重要靶点。这些数据与体外 DNA 结合研究表明，甲状腺激素受体可能具有双重调节作用：在激素存在的情况下，它们充当 TRE 特异性转录激活剂；在激素存在的情况下，它们充当 TRE 特异性转录激活剂；然而，在没有激素的情况下，它们可以充当 TRE 特异性阻遏物。
BOTH thyroid hormone (T3) and retinoic acid signal essential steps in development, differentiation and morphogenesis. Specific nuclear receptors for these ligands have recently been cloned1-8. Previously we have noted a close homology between the DNA-binding domains of the ε-retinoic acid receptor (RAR-ε, also designated RAR-β), the thyroid hormone receptors and the oes-trogen receptor2,9. We have now found that RAR-ε is very efficient at inducing transcription from two distinct thyroid-hormone responsive elements (TREs). Transcription induced by ligand-activated RAR-ε from a TRE can, however, be repressed by thyroid-hormone receptor in the absence of its ligand. Conversely, in the presence of its ligand, thyroid-hormone receptor will activate tran-scription from a TRE irrespective of the presence of unbound RAR. The use of hybrid receptors has shown that the DNA-binding domain of RAR is the essential target for inhibition by thyroid-hormone receptors. These data, together with in vitro DNA-binding studies, suggest that thyroid-hormone receptors may have dual regulatory roles: in the presence of hormone they function as TRE-specific transcriptional activators; in the absence of hormone, however, they can function as TRE-specific repressers.