Chambon P
Institut de Génétique et de Biologie Moleculaire et Cellulaire, CNRS/INSERUM/ULP, Collège de France, Strasbourg, France.
FASEB J. 1996 Jul;10(9):940-54.
Retinoids play an important role in development, differentiation, and homeostasis. The discovery of retinoid receptors belonging to the superfamily of nuclear ligand-activated transcriptional regulators has revolutionized our molecular understanding as to how these structurally simple molecules exert their pleiotropic effects. Diversity in the control of gene expression by retinoid signals is generated through complexity at different levels of the signaling pathway. A major source of diversity originates from the existence of two families of retinoid acid (RA) receptors (R), the RAR isotypes (alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma), and their numerous isoforms, which bind as RXR/RAR heterodimers to the polymorphic cis-acting response elements of RA target genes. The possibility of cross-modulation (cross-talk) with cell-surface receptors signaling pathways, as well as the finding that RARs and RXRs interact with multiple putative coactivators and/or corepressors, generates additional levels of complexity for the array of combinatorial effects that underlie the pleiotropic effects of retinoids. This review focuses on recent developments, particularly in the area of structure-function relationships.
维甲酸在发育、分化和体内平衡中发挥着重要作用。属于核配体激活转录调节因子超家族的维甲酸受体的发现，彻底改变了我们对这些结构简单的分子如何发挥其多效性作用的分子理解。维甲酸信号对基因表达的控制多样性是通过信号通路不同水平的复杂性产生的。多样性的一个主要来源是存在两类维甲酸（RA）受体（R），即RAR同型异构体（α、β和γ）和三种RXR同型异构体（α、β和γ），以及它们众多的亚型，它们以RXR/RAR异二聚体形式与RA靶基因的多态性顺式作用反应元件结合。与细胞表面受体信号通路进行交叉调节（相互作用）的可能性，以及RAR和RXR与多种假定的共激活剂和/或共抑制剂相互作用的发现，为构成维甲酸多效性作用基础的一系列组合效应增加了额外的复杂程度。本综述重点关注近期的进展，特别是在结构 - 功能关系领域。
