Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology.

Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology.
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DOI:
10.1007/s00018-009-0098-z
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发表时间:
2009-11
影响因子:
8
通讯作者:
Chrousos, George P.
Chrousos, George P.
中科院分区:
生物学1区
文献类型:
--
作者:
Kino, Tomoshige;Su, Yan A.;Chrousos, George P.

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人糖皮质激素受体(GR)基因通过交替使用特定外显子9α和9β表达两种剪接异构体α和α。与经典的受体GRα不同,GRβ介导了糖皮质激素的大部分已知作用,其功能在很大程度上尚未被探索。由于新开发的方法,如微阵列和水母荧光蛋白,我们和其他人最近发现了GRβ的新功能。事实上,这种神秘的GR亚型除了对GRα介导的转录活性产生众所周知的显性负面影响外,还对大量基因的转录活性产生积极和消极的影响,其中大多数基因对糖皮质激素不敏感。最近的一篇报道表明,GRβ的“配体结合域”是活性的,形成了一个功能性的配体结合口袋,与合成的化合物RU486有关。本文就GRβ的功能、作用机制及其病理意义作一综述。
The human glucocorticoid receptor (GR) gene expresses two splicing isoforms α and β through alternative use of specific exons 9α and 9α. In contrast to the classic receptor GRα, which mediates most of the known actions of glucocorticoids, the functions of GRβ have been largely unexplored. Owing to newly developed methods, such as microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRβ. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRα-mediated transcriptional activity. A recent report suggested that the “ligand-binding domain” of GRβ is active, forming a functional ligand-binding pocket, associated with the synthetic compound RU 486. In this review, we discuss the functions of GRβ, its mechanisms of action, and its pathologic implications.
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