Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model?

Current Topics in Developmental Biology
Guillaume HolzerVincent Laudet

Abstract

Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that modulate a wide variety of physiological functions in a ligand-dependent manner. The first NRs were discovered as receptors of well-known hormones such as 17β-estradiol, corticosteroids, or thyroid hormones. In these cases a direct activation of the receptor transcriptional activity by a very specific ligand, with nanomolar affinity, was demonstrated, providing a strong conceptual framework to understand the mechanism of action of these hormones. However, the discovery that some NRs are able to bind different ligands with micromolar affinity was a first sign that the univocal relationship between a specific receptor (e.g., TR) and a specific ligand (e.g., thyroid hormone) should not be generalized to the whole family. These discussions about the nature of NR ligands have been reinforced by the study of the hormone/receptor couple evolution. Indeed when the ligand is not a protein but a small molecule derived from a biochemical pathway, a simple coevolution mechanism between the ligand and the receptor cannot operate. We and others have recently shown that the ligands acting for a given NR early on during evolution were often different from the c...Continue Reading

Citations

Jan 26, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew J AnnaloraPatrick L Iversen
Apr 2, 2019·Frontiers in Endocrinology·Iván LazcanoAurea Orozco
Jan 15, 2021·Genes·Angelica MiglioliRémi Dumollard
Mar 7, 2018·The Journal of Steroid Biochemistry and Molecular Biology·Adam M ReitzelAnn M Tarrant
Apr 27, 2019·Molecular and Cellular Endocrinology·Wojciech KrężelAngel R de Lera
Jan 22, 2020·Molecular and Cellular Endocrinology·Virginie Cuvillier-Hot, Alain Lenoir
Mar 14, 2021·Structure·Jinsai Shang, Douglas J Kojetin

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