Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer
Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer
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DOI：
10.1128/mcb.22.16.5782-5792.2002
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发表时间：
2002-08-01
影响因子：
5.3
通讯作者：
Samuels, HH
中科院分区：
文献类型：
--
作者：
Li, DS;Li, T;Samuels, HH
甲状腺激素/类维生素A受体亚家族（11型核受体）的许多成员与类维生素A X受体（RXR）作为异二聚体发挥作用。在被称为允许的二聚体中，如过氧化物酶体增殖物激活受体/RXR，两种配偶体都可以结合同源配体并引发配体依赖性反式激活。相比之下，甲状腺激素受体（TR）/RXR异二聚体被认为是非允许的，其中RXR被认为不能与配体结合，通常被称为沉默伴侣。在这份报告中，我们使用了一个敏感的去阻遏测定系统，我们以前开发重新检查TR/RXR的相互关系。我们提供的功能证据表明，在TR/RXR异二聚体，RXR组件可以结合其在体内的配体。通过RXR的配体结合似乎不直接激活TR/RXR异二聚体;相反，它导致细胞抑制剂/辅阻遏物与其TR配偶体的（至少瞬时或动态）解离，因此可能用于调节未配体的TR介导的阻遏和/或配体的TR介导的激活。我们的研究结果反对目前TR/RXR异二聚体中RXR的沉默伴侣模型，并揭示了TR和RXR之间交叉调节的一个意想不到的方面。
Many members of the thyroid hormone/retinoid receptor subfamily (type 11 nuclear receptors) function as heterodimers with the retinoid X receptor (RXR). In beterodimers which are referred to as permissive, such as peroxisome proliferator activated receptor/RXR, both partners can bind cognate ligands and elicit ligand-dependent transactivation. In contrast, the thyroid hormone receptor (TR)/RXR heterodimer is believed to be nonpermissive, where RXR is thought to be incapable of ligand binding and is often referred to as a silent partner. In this report, we used a sensitive derepression assay system that we developed previously to reexamine the TR/RXR interrelationship. We provide functional evidence suggesting that in a TR/RXR heterodimer, the RXR component can bind its ligand in vivo. Ligand binding by RXR does not appear to directly activate the TR/RXR heterodimer; instead, it leads to a (at least transient or dynamic) dissociation of a cellular inhibitor(s)/corepressor(s) from its TR partner and thus may serve to modulate unliganded TR-mediated repression and/or liganded TR-mediated activation. Our results argue against the current silent-partner model for RXR in the TR/RXR heterodimer and reveal an unexpected aspect of cross regulation between TR and RXR.