Department of Pathology and Molecular Medicine, Queens University, Kingston, Ontario, Canada.
Institut de Génétique et de Biologie Moléculaire et Cellulaire (I.G.B.M.C.), Illkirch, France.
J Mol Endocrinol. 2022 Oct 11;69(4):T13-T24. doi: 10.1530/JME-22-0097. Print 2022 Nov 1.
For almost a century, vitamin A has been known as a nutrient critical for normal development, differentiation, and homeostasis; accordingly, there has been much interest in understanding its mechanism of action. This review is about the discovery of specific receptors for the vitamin A derivative, retinoic acid (RA), which launched extensive molecular, genetic, and structural investigations into these new members of the nuclear receptor superfamily of transcriptional regulators. These included two families of receptors, the RAR isotypes (α, β, and γ) along with three RXR isotypes (α, β, and γ), which bind as RXR/RAR heterodimers to cis-acting response elements of RA target genes to generate a high degree of complexity. Such studies have provided deep molecular insight into how the widespread pleiotropic effects of RA can be generated.
近一个世纪以来，维生素 A 一直被认为是一种对正常发育、分化和内稳态至关重要的营养物质；因此，人们非常感兴趣地了解其作用机制。这篇综述是关于维生素 A 衍生物视黄酸 (RA) 的特定受体的发现，这为核受体超家族转录调节剂的这些新成员展开了广泛的分子、遗传和结构研究。这些受体包括两类，即 RAR 同工型（α、β 和 γ）和三种 RXR 同工型（α、β 和 γ），它们作为 RXR/RAR 异二聚体结合到 RA 靶基因的顺式作用反应元件上，从而产生高度的复杂性。这些研究为 RA 的广泛多效性效应如何产生提供了深刻的分子见解。
