Kadiyala Vineela, Smith Catharine L
Department of Pharmacology and Toxicology, College of Pharmacy (V.K., C.L.S.), Department of Chemistry and Biochemistry, College of Science (V.K.), University of Arizona, Tucson Arizona 85721.
Mol Endocrinol. 2014 May;28(5):607-21. doi: 10.1210/me.2014-1002. Epub 2014 Mar 19.
Lysine deacetylases have been known to regulate nuclear receptor function for many years. In the unliganded state, nuclear receptors that form heterodimers with retinoid X receptors, such as the retinoic acid and thyroid hormone receptors, associate with deacetylases to repress target genes. In the case of steroid receptors, binding of an antagonist ligand was initially reported to induce association of deacetylases to prevent activation of target genes. Since then, deacetylases have been shown to have diverse functions in steroid receptor signaling, from regulating interactions with molecular chaperones to facilitating their ability to activate transcription. The purpose of this review is to summarize recent studies on the role of deacetylases in steroid receptor signaling, which show deacetylases to be highly versatile regulators of steroid receptor function.
多年来,人们已经知道赖氨酸脱乙酰酶可调节核受体功能。在未结合配体的状态下,与视黄酸X受体形成异二聚体的核受体,如维甲酸受体和甲状腺激素受体,会与脱乙酰酶结合以抑制靶基因。就类固醇受体而言,最初有报道称拮抗剂配体的结合会诱导脱乙酰酶的结合,以防止靶基因的激活。从那时起,脱乙酰酶已被证明在类固醇受体信号传导中具有多种功能,从调节与分子伴侣的相互作用到促进其激活转录的能力。本综述的目的是总结最近关于脱乙酰酶在类固醇受体信号传导中作用的研究,这些研究表明脱乙酰酶是类固醇受体功能的高度通用的调节剂。