Fondell J D, Ge H, Roeder R G
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8329-33. doi: 10.1073/pnas.93.16.8329.
Transcriptional regulation by nuclear hormone receptors is thought to involve interactions with putative cofactors that may potentiate receptor function. Here we show that human thyroid hormone receptor alpha purified from HeLa cells grown in the presence of thyroid hormone (T3) is associated with a group of distinct nuclear proteins termed thyroid hormone receptor-associated proteins (TRAPs). In an in vitro system reconstituted with general initiation factors and cofactors (and in the absence of added T3), the "liganded" thyroid hormone receptor (TR)/TRAP complex markedly activates transcription from a promoter template containing T3-response elements. Moreover, whereas the retinoid X receptor is not detected in the TR/TRAP complex, its presence is required for the function of the complex. In contrast, human thyroid hormone receptor alpha purified from cells grown in the absence of T3 lacks the TRAPs and effects only a low level of activation that is dependent on added ligand. These findings demonstrate the ligand-dependent in vivo formation of a transcriptionally active TR-multisubunit protein complex and suggest a role for TRAPs as positive coactivators for gene-specific transcriptional activation.
核激素受体的转录调控被认为涉及与可能增强受体功能的假定辅因子的相互作用。在这里，我们表明，从在甲状腺激素（T3）存在下生长的HeLa细胞中纯化的人甲状腺激素受体α与一组称为甲状腺激素受体相关蛋白（TRAPs）的不同核蛋白相关联。在用通用起始因子和辅因子重构的体外系统中（并且在没有添加T3的情况下），“配体化”的甲状腺激素受体（TR）/TRAP复合物显著激活来自含有T3反应元件的启动子模板的转录。此外，虽然在TR/TRAP复合物中未检测到维甲酸X受体，但其存在是复合物功能所必需的。相反，从在没有T3的情况下生长的细胞中纯化的人甲状腺激素受体α缺乏TRAPs，并且仅产生依赖于添加配体的低水平激活。这些发现证明了转录活性TR-多亚基蛋白复合物在体内的配体依赖性形成，并表明TRAPs作为基因特异性转录激活的正性辅激活因子的作用。
