Carosa E, Fanelli A, Ulisse S, Di Lauro R, Rall J E, Jannini E A
Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy.
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11152-7. doi: 10.1073/pnas.95.19.11152.
Nuclear hormone receptors comprise a large family of zinc finger transcription factors, some with hydrophobic ligands, such as thyroid hormone, vitamin D, steroids, etc., and others for which no ligand has been found. Thyroid hormone receptors (TRs) generally are considered to be confined to the vertebrata that possess a thyroid gland. Tunicates represent the most primitive of the chordates, and there are data supporting a role for thyroid hormone in their metamorphosis, but no data are available on TRs in this genus; hence, we have studied Ciona intestinalis. Screening of a Ciona library with the DNA binding domain of Xenopus laevis TR (xTR) resulted in the isolation of a nuclear hormone receptor, C. intestinalis nuclear receptor 1 (CiNR1). CiNR1 is similar to TRs of more evolved species with a conserved DNA binding domain whereas the ligand binding domain shows poor homology to vertebrate sequences. The C-terminal part of CiNR1 spans approximately 200 amino acids more than other TRs, lacks the AF2 transactivation domain, and is not able to bind triiodothyronine. Phylogenetically, CiNR1 appears to be close to the common ancestral gene of TRs. Expression of CiNR1 was limited to the developing embryo and the larval stage, which suggests a role during development and metamorphosis. In transfection experiments, CiNR1 down-regulated basal transcription of a reporter gene driven by the TR palindrome responsive element. When CiNR1 was cotransfected with chicken TRalpha, it attenuated the normal thyroid hormone response in a dominant negative fashion. This attenuation required the C-terminal portion of the molecule.
核激素受体构成了一个由锌指转录因子组成的大家族，其中一些受体具有疏水配体，如甲状腺激素、维生素D、类固醇等，而另一些受体尚未发现配体。甲状腺激素受体（TRs）通常被认为局限于拥有甲状腺的脊椎动物。被囊动物是最原始的脊索动物，有数据支持甲状腺激素在其变态过程中的作用，但该属中关于TRs的数据尚无；因此，我们研究了玻璃海鞘。用非洲爪蟾TR（xTR）的DNA结合结构域筛选玻璃海鞘文库，结果分离出一种核激素受体，即玻璃海鞘核受体1（CiNR1）。CiNR1与进化程度更高的物种的TRs相似，具有保守的DNA结合结构域，而配体结合结构域与脊椎动物序列的同源性较差。CiNR1的C末端部分比其他TRs大约多200个氨基酸，缺乏AF2反式激活结构域，并且不能结合三碘甲状腺原氨酸。从系统发育上看，CiNR1似乎接近TRs的共同祖先基因。CiNR1的表达仅限于发育中的胚胎和幼虫阶段，这表明其在发育和变态过程中发挥作用。在转染实验中，CiNR1下调了由TR回文反应元件驱动的报告基因的基础转录。当CiNR1与鸡TRα共转染时，它以显性负性方式减弱正常的甲状腺激素反应。这种减弱需要分子的C末端部分。
