Cohen R N, Wondisford F E, Hollenberg A N
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Mol Endocrinol. 1998 Oct;12(10):1567-81. doi: 10.1210/mend.12.10.0188.
The nuclear corepressor (NCoR) binds to the thyroid hormone receptor (TR) in the absence of ligand. NCoR-TR interactions are mediated by two interaction domains in the C-terminal portion of NCoR. Binding of NCoR to TR results in ligand-independent repression on positive thyroid hormone response elements. The interactions between NCoR interaction domains and TR on DNA response elements, however, have not been well characterized. We have found that both interaction domains are capable of binding TR on thyroid hormone response elements. In addition, the NCoR interaction domains interact much more strongly with the TR than those present in the silencing mediator of retinoic acid and TRs (SMRT). Furthermore, deletion of either NCoR interaction domain does not significantly impair ligand-independent effects on positive or negative thyroid hormone response elements. Finally, both NCoR interaction domains appear to preferentially bind TR homodimer over TR-retinoid X receptor heterodimer in electrophoretic mobility shift assays. These data suggest that either NCoR interaction domain is capable of mediating the ligand-independent effects of TR on positive and negative thyroid hormone response elements.
在没有配体的情况下，核共抑制因子（NCoR）与甲状腺激素受体（TR）结合。NCoR与TR的相互作用由NCoR C末端部分的两个相互作用结构域介导。NCoR与TR的结合导致对甲状腺激素阳性反应元件的非配体依赖性抑制。然而，NCoR相互作用结构域与DNA反应元件上的TR之间的相互作用尚未得到充分表征。我们发现，这两个相互作用结构域都能够在甲状腺激素反应元件上结合TR。此外，NCoR相互作用结构域与TR的相互作用比视黄酸和TR沉默介质（SMRT）中的相互作用结构域与TR的相互作用要强得多。此外，删除任何一个NCoR相互作用结构域都不会显著损害对甲状腺激素阳性或阴性反应元件的非配体依赖性作用。最后，在电泳迁移率变动分析中，两个NCoR相互作用结构域似乎都优先结合TR同二聚体而非TR-视黄酸X受体异二聚体。这些数据表明，任一NCoR相互作用结构域都能够介导TR对甲状腺激素阳性和阴性反应元件的非配体依赖性作用。
