Jones B B, Ohno C K, Allenby G, Boffa M B, Levin A A, Grippo J F, Petkovich M
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Mol Cell Biol. 1995 Oct;15(10):5226-34. doi: 10.1128/MCB.15.10.5226.
Retinoid X receptors (RXRs), along with retinoic acid (RA) receptors (RARs), mediate the effects of RA on gene expression. Three subtypes of RXRs (alpha, beta, and gamma) which bind to and are activated by the 9-cis stereoisomer of RA have been characterized. They activate gene transcription by binding to specific sites on DNA as homodimers or as heterodimers with RARs and other related nuclear receptors, including the vitamin D receptor, thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors. Two additional RXR subtypes (delta and epsilon) isolated from zebra fish cDNA libraries are described here; although both subtypes form DNA-binding heterodimers with RARs and TR, neither binds 9-cis RA, and both are transcriptionally inactive on RXR response elements. In cotransfection studies with TR, the delta subtype was found to function in a dominant negative manner, while the epsilon subtype had a slight stimulatory effect on thyroid hormone (T3)-dependent transcriptional activity. The discovery of these two novel receptors in zebra fish expands the functional repertoire of RXRs to include ligand-independent and dominant negative modulation of type II receptor function.
维甲酸X受体（RXRs）与维甲酸（RA）受体（RARs）共同介导RA对基因表达的作用。已鉴定出RXRs的三种亚型（α、β和γ），它们可与RA的9-顺式立体异构体结合并被其激活。它们通过作为同二聚体或与RARs及其他相关核受体（包括维生素D受体、甲状腺激素受体（TRs）和过氧化物酶体增殖物激活受体）形成异二聚体，结合到DNA上的特定位点来激活基因转录。本文描述了从斑马鱼cDNA文库中分离出的另外两种RXR亚型（δ和ε）；尽管这两种亚型都能与RARs和TR形成DNA结合异二聚体，但它们都不与9-顺式RA结合，并且在RXR反应元件上都没有转录活性。在与TR的共转染研究中，发现δ亚型以显性负性方式发挥作用，而ε亚型对甲状腺激素（T3）依赖的转录活性有轻微的刺激作用。在斑马鱼中发现的这两种新型受体扩展了RXRs的功能范围，使其包括对II型受体功能的非配体依赖性和显性负性调节。
