Activation of the orphan receptor RIP14 by retinoids.
Activation of the orphan receptor RIP14 by retinoids.
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类维生素A激活孤儿受体RIP14。
DOI：
10.1073/pnas.94.15.7909
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发表时间：
1997
影响因子：
11.1
通讯作者：
Moore,DD
中科院分区：
文献类型：
--
作者：
Zavacki,AM;Lehmann,JM;Seol,W;Willson,TM;Kliewer,SA;Moore,DD
类维生素A是发育中和成年动物中多种过程的重要调节剂。这些作用被认为是由视黄酸 (RA) 受体和类视黄醇 X 受体 (RXR) 介导的。我们已经鉴定出另一种视黄酸激活受体，它既不是视黄酸受体也不是 RXR。 RXR 相互作用蛋白 14 (RIP14) 是最近描述的核受体超家族的孤儿成员，可以被全反式 RA (tRA) 或合成类视黄醇 TTNPB {[E]-4-[2-(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)丙烯-1-基]苯甲酸激活 酸}。 RIP14 与 RXR 形成异二聚体结合到 DNA 上。在 tRA 或 TTNPB 存在的情况下，添加 9-cis-RA 或 RXR 特异性激动剂 LG1069 {4-[1-(3,5,5,8,8-五甲基-5,6,7,8-四氢-2-萘基)乙烯基]苯甲酸}会导致额外的激活。配体依赖性转录激活功能的突变表明TTNPB激活RIP14-RXR异二聚体的RIP14成分，9-cis-RA和LG1069激活RXR，并且tRA通过RIP14和RXR激活。尽管 tRA 或 TTNPB 可以非常有效地激活 RIP14，但需要相对较高浓度的这些化合物，并且使用多种方法都没有获得任何化合物直接结合的证据。这些结果表明 RIP14 是一种尚未鉴定的类维生素A代谢物的受体。
Retinoids are crucial regulators of a wide variety of processes in both developing and adult animals. These effects are thought to be mediated by the retinoic acid (RA) receptors and the retinoid X receptors (RXRs). We have identified an additional retinoid-activated receptor that is neither a retinoic acid receptors nor an RXR. RXR-interacting protein 14 (RIP14), a recently described orphan member of the nuclear receptor superfamily, can be activated by either all-trans-RA (tRA) or the synthetic retinoid TTNPB {[E]-4-[2-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)propen-1-yl]benzoic acid}. RIP14 binds to DNA as a heterodimer with RXR. In the presence of either tRA or TTNPB, the addition of 9-cis-RA or the RXR-specific agonist LG1069 {4-[1-(3, 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tertrahydro-2-naphthyl)ethenyl]benzoic acid} results in additional activation. Mutations of the ligand-dependent transcriptional activation functions indicate that TTNPB activates the RIP14 component of the RIP14–RXR heterodimer, that 9-cis-RA and LG1069 activate RXR, and that tRA activates via both RIP14 and RXR. Despite the very effective activation of RIP14 by tRA or TTNPB, relatively high concentrations of these compounds are required, and no evidence for direct binding of either compound was obtained using several approaches. These results suggest that RIP14 is the receptor for an as-yet-unidentified retinoid metabolite.