RORα augments thyroid hormone receptor-mediated transcriptional activation
RORα augments thyroid hormone receptor-mediated transcriptional activation
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DOI：
10.1210/en.140.3.1356
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发表时间：
1999-03-01
期刊：
影响因子：
4.8
通讯作者：
Chin, WW
中科院分区：
文献类型：
--
作者：
Koibuchi, N;Liu, Y;Chin, WW
本研究旨在阐明孤儿核激素受体ROR α在甲状腺激素（TH）受体（TR）介导的TH反应元件（TRE）转录中的作用。使用多种TREs[即F2（鸡溶菌酶TRE）， DR4（直接重复）和回文TRE]以及TR和ROR α 1进行瞬时转染研究。当ROR α 1和TR共转染到CV1细胞时，ROR α 1增强了配体TR对所有被测试的TREs的反转录激活，而不影响未配体TR的基础抑制。另一方面，通过电泳迁移率转移实验，尽管ROR α α以单体形式结合所有被测试的TREs，但在除rα α 1外的所有TREs上没有（或弱）观察到TR和ROR α 1异源二聚体的形成。当假定的ROR-response元素存在时。ROR α 1对不含TRE的ROR-response元件的转激活不被TR增强。ROR α 1对TREs的作用是独特的，因为其他核激素受体（如维生素D受体）可能竞争性地与TRE结合以发挥主要的负功能，而ROR α 1增强了TR作用。这些结果表明，ROR α 1可能会改变配体TR对th反应基因的作用。由于TR和ROR α在小脑浦肯野细胞中共表达，围产期甲状腺功能减退动物和ROR α被破坏的动物也表现出类似的这种细胞类型异常，这两种受体之间的串导可能在浦肯野细胞分化中起关键作用。
This study is designed to clarify the role of an orphan nuclear hormone receptor, ROR alpha, on thyroid hormone (TH) receptor (TR)-mediated transcription on a TH-response element (TRE). A transient transfection study using various TREs [i.e., F2 (chick lysozyme TRE), DR4 (direct repeat), and palindrome TRE] and TR and ROR alpha 1 was performed. When ROR alpha 1 and TR were cotransfected into CV1 cells, ROR alpha 1 enhanced the transactivation by liganded-TR on all TREs tested without an effect on basal repression by unliganded TR. By electrophoretic mobility shift assay, on the other hand, although ROR alpha bound to all TREs tested as a monomer, no (or weak) TR and ROR alpha 1 heterodimer formation was observed on various TREs except; when a putative ROR-response element was present. The transactivation by ROR alpha 1 on a ROR-response element, which does not contain a TRE, was not enhanced by TR. The effect of ROR alpha 1 on the TREs is unique, because, whereas other nuclear hormone receptors (such as vitamin D receptor) may competitively bind to TRE to exert dominant negative function, ROR alpha 1 augmented TR action. These results indicate that ROR alpha 1 may modify the effect of liganded TR on TH-responsive genes. Because TR and ROR alpha are coexpressed in cerebellar Purkinje cells, and perinatal hypothyroid animals and ROR alpha-disrupted animals show similar abnormalities of this cell type, cross-talk between these two receptors may play a critical role in Purkinje cell differentiation.