Forman B M, Goode E, Chen J, Oro A E, Bradley D J, Perlmann T, Noonan D J, Burka L T, McMorris T, Lamph W W, Evans R M, Weinberger C
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Cell. 1995 Jun 2;81(5):687-93. doi: 10.1016/0092-8674(95)90530-8.
Nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that mediate the transcriptional activities of steroids, retinoids, and thyroid hormones. A growing number of related proteins have been identified that possess the structural features of hormone receptors, but that lack known ligands. Known as orphan receptors, these proteins represent targets for novel signaling molecules. We have isolated a mammalian orphan receptor that forms a heterodimeric complex with the retinoid X receptor. A screen of candidate ligands identified farnesol and related metabolites as effective activators of this complex. Farnesol metabolites are generated intracellularly and are required for the synthesis of cholesterol, bile acids, steroids, retinoids, and farnesylated proteins. Intermediary metabolites have been recognized as transcriptional regulators in bacteria and yeast. Our results now suggest that metabolite-controlled intracellular signaling systems are utilized by higher organisms.
核激素受体构成了一个配体调节转录因子超家族，介导类固醇、视黄酸和甲状腺激素的转录活性。越来越多具有激素受体结构特征但缺乏已知配体的相关蛋白被鉴定出来。这些被称为孤儿受体的蛋白代表了新型信号分子的作用靶点。我们分离出了一种与视黄酸X受体形成异二聚体复合物的哺乳动物孤儿受体。对候选配体的筛选确定了法尼醇及相关代谢产物是该复合物的有效激活剂。法尼醇代谢产物在细胞内生成，是胆固醇、胆汁酸、类固醇、视黄酸和法尼基化蛋白合成所必需的。中间代谢产物在细菌和酵母中已被认为是转录调节因子。我们的结果表明高等生物利用代谢物控制的细胞内信号系统。
