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首页> 外文期刊>Molecular and Cellular Biology >Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors.
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Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors.

机译：过氧化物酶体增殖物激活受体和视黄酸受体差异控制类视黄醇X受体异二聚体与配体，共激活剂和共抑制因子的相互作用。

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As the obligate member of most nuclear receptor heterodimers, retinoid X receptors (RXRs) can potentially perform two functions: cooperative binding to hormone response elements and coordinate regulation of target genes by RXR ligands. In this paper we describe allosteric interactions between RXR and two heterodimeric partners, retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs); RARs and PPARs prevent and permit activation by RXR-specific ligands, respectively. By competing for dimerization with RXR on response elements consisting of direct-repeat half-sites spaced by 1 bp (DR1 elements), the relative abundance of RAR and PPAR determines whether the RXR signaling pathway will be functional. In contrast to RAR, which prevents the binding of RXR ligands and recruits the nuclear receptor corepressor N-CoR, PPAR permits the binding of SRC-1 in response to both RXR and PPAR ligands. Overexpression of SRC-1 markedly potentiates ligand-dependent transcription by PPARgamma, suggesting that SRC-1 serves as a coactivator in vivo. Remarkably, the ability of RAR to both block the binding of ligands to RXR and interact with corepressors requires the CoR box, a structural motif residing in the N-terminal region of the RAR ligand binding domain. Mutations in the CoR box convert RAR from a nonpermissive to a permissive partner of RXR signaling on DR1 elements. We suggest that the differential recruitment of coactivators and corepressors by RAR-RXR and PPAR-RXR heterodimers provides the basis for a transcriptional switch that may be important in controlling complex programs of gene expression, such as adipocyte differentiation.
机译：作为大多数核受体异二聚体的排他性成员，类视黄醇X受体（RXR）可能具有两项功能：与激素反应元件的协同结合以及通过RXR配体协调靶基因的调控。在本文中，我们描述了RXR与两个异二聚体伴侣，视黄酸受体（RAR）和过氧化物酶体增殖物激活受体（PPAR）之间的变构相互作用。 RAR和PPAR分别阻止并允许RXR特异性配体激活。通过在由间隔为1 bp的直接重复半位点组成的响应元件（DR1元件）上与RXR竞争二聚化，RAR和PPAR的相对丰度决定了RXR信号通路是否起作用。与RAR阻止RXR配体的结合并募集核受体共受体N-CoR相比，PPAR可以响应RXR和PPAR配体而结合SRC-1。 SRC-1的过表达显着增强了PPARgamma的配体依赖性转录，表明SRC-1在体内起着共激活剂的作用。值得注意的是，RAR既能阻止配体与RXR结合又能与共抑制因子相互作用，这需要CoR盒，即位于RAR配体结合域N端区域的结构基序。 CoR框中的突变将RAR从DR1元素上的RXR信号的非许可伙伴转换为许可伙伴。我们建议，RAR-RXR和PPAR-RXR异二聚体对共激活因子和共核心因子的差异募集提供了转录开关的基础，该转录开关可能在控制复杂的基因表达程序（例如脂肪细胞分化）中很重要。

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