The origin and functions of multiple human glucocorticoid receptor isoforms
The origin and functions of multiple human glucocorticoid receptor isoforms
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DOI：
10.1196/annals.1321.008
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Cidlowski, JA
中科院分区：
文献类型：
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作者：
Lu, NZ;Cidlowski, JA
糖皮质激素是生命所必需的，对人类健康和疾病的各个方面都是必不可少的。糖皮质激素的作用是由糖皮质激素受体(GR)介导的，GR结合糖皮质激素，调节基因表达、细胞信号和体内平衡。几十年的研究主要集中在GR的一种亚型GRα的作用机制上。然而，近年来，越来越多的人GR(HGR)亚型被报道。从该实验室和其他实验室获得的证据表明，单个HGR基因通过突变和/或多态性、转录本选择性剪接和选择性翻译起始产生多种HGR亚型。每一个HGR蛋白又会受到各种翻译后修饰，翻译后修饰的性质和程度会影响受体的功能。我们在这里总结了产生和修饰各种HGR亚型的过程，重点是那些影响HGR调节靶基因能力的过程。我们推测，细胞内独特的受体组成和相对受体比例决定了对糖皮质激素的特异性反应。一些异构体的不受控制的表达，例如hGRβ，已被认为与多种疾病有关。
Glucocorticoid hormones are necessary for life and are essential in all aspects of human health and disease. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which binds glucocorticoid hormones and regulates gene expression, cell signaling, and homeostasis. Decades of research have focused on the mechanisms of action of one isoform of GR, GRalpha. However, in recent years, increasing numbers of human GR (hGR) isoforms have been reported. Evidence obtained from this and other laboratories indicates that multiple hGR isoforms are generated from one single hGR gene via mutations and/or polymorphisms, transcript alternative splicing, and alternative translation initiation. Each hGR protein, in turn, is subject to a variety of posttranslational modifications, and the nature and degree of posttranslational modification affect receptor function. We summarize here the processes that generate and modify various hGR isoforms with a focus on those that impact the ability of hGR to regulate target genes. We speculate that unique receptor compositions and relative receptor proportions within a cell determine the specific response to glucocorticoids. Unchecked expression of some isoforms, for example hGRbeta, has been implicated in various diseases.