Department of Genetics, Center for Molecular Medicine, University of Georgia, Athens, GA 30602, USA.
Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
Cells. 2020 Dec 4;9(12):2606. doi: 10.3390/cells9122606.
Nuclear hormone receptors are a family of transcription factors regulated by small molecules derived from the endogenous metabolism or diet. There are forty-eight nuclear hormone receptors in the human genome, twenty of which are still orphans. In this review, we make a brief historical journey from the first observations by Berthold in 1849 to the era of orphan receptors that began with the sequencing of the genome in 1998. We discuss the evolution of nuclear hormone receptors and the putative ancestral ligands as well as how the ligand universe has expanded over time. This leads us to define four classes of metabolites-fatty acids, terpenoids, porphyrins and amino acid derivatives-that generate all known ligands for nuclear hormone receptors. We conclude by discussing the ongoing efforts to identify new classes of ligands for orphan receptors.
核激素受体是一类受小分子调节的转录因子，这些小分子来源于内源性代谢或饮食。人类基因组中有四十八个核激素受体，其中二十个仍然是孤儿受体。在这篇综述中，我们简要回顾了从 1849 年 Berthold 的最初观察到 1998 年基因组测序开始的孤儿受体时代的历史进程。我们讨论了核激素受体的进化以及假定的祖先配体，以及配体宇宙是如何随着时间的推移而扩展的。这使我们能够定义四类代谢产物——脂肪酸、萜类化合物、卟啉和氨基酸衍生物——它们产生了所有已知的核激素受体配体。最后，我们讨论了为孤儿受体识别新配体类别的持续努力。
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