Piskunov Aleksandr, Al Tanoury Ziad, Rochette-Egly Cécile
IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U964, CNRS, UMR7104, Université de Strasbourg, 1 rue Laurent Fries, BP 10142, 67404, Illkirch Cedex, France,
Subcell Biochem. 2014;70:103-27. doi: 10.1007/978-94-017-9050-5_6.
The nuclear retinoic acid receptors (RAR α, β and γ) and their isoforms are ligand-dependent regulators of transcription Transcription , which mediate the effects of all-trans retinoic acid (RA), the active endogenous metabolite of Vitamin A. They heterodimerize with Retinoid X Receptors (RXRs α, β and γ), and regulate the expression of a battery of target genes Target genes involved in cell growth and differentiation Differentiation . During the two last decades, the description of the crystallographic structures of RARs, the characterization of the polymorphic response elements of their target genes Target genes , and the identification of the multiprotein complexes involved in their transcriptional activity have provided a wealth of information on their pleiotropic effects. However, the regulatory scenario became even more complicated once it was discovered that RARs are phosphoproteins and that RA can activate kinase signaling cascades via a pool of RARs present in membrane lipid rafts. Now it is known that these RA-activated kinases Kinases translocate to the nucleus where they phosphorylate RARs and other retinoid signaling factors. The phosphorylation Phosphorylation state of the RARs dictates whether the transcriptional programs which are known to be induced by RA are facilitated and/or switched on. Thus, kinase signaling pathways appear to be crucial for fine-tuning the appropriate physiological activity of RARs.
核视黄酸受体（RARα、β和γ）及其亚型是转录的配体依赖性调节因子，介导维生素A的活性内源性代谢产物全反式视黄酸（RA）的作用。它们与类视黄醇X受体（RXRα、β和γ）形成异二聚体，并调节一系列参与细胞生长和分化的靶基因的表达。在过去的二十年中，RARs晶体结构的描述、其靶基因多态性反应元件的表征以及参与其转录活性的多蛋白复合物的鉴定，为其多效性作用提供了丰富的信息。然而，一旦发现RARs是磷蛋白，并且RA可以通过存在于膜脂筏中的一组RARs激活激酶信号级联反应，调控情况就变得更加复杂。现在已知这些RA激活的激酶会转移到细胞核，在那里它们使RARs和其他类视黄醇信号因子磷酸化。RARs的磷酸化状态决定了已知由RA诱导的转录程序是被促进和/或开启。因此，激酶信号通路似乎对于微调RARs的适当生理活性至关重要。
