Corticosteroid Receptors, Their Chaperones and Cochaperones: How Do They Modulate Adipogenesis?

J. Toneatto, N. Charó, A. Naselli, Melina Muñoz-Bernart, A. Lombardi, G. Piwien-Pilipuk
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引用次数: 1

Abstract

It is well known that glucocorticoids and mineralocorticoids are part of the list of hormones that control adipogenesis as well as different aspects of the physiology of the adipose tissue. Their actions are mediated through their binding to the glucocorticoid and the mineralocorticoid receptors (GR and MR, respectively), in complex with heat shock proteins (Hsps) and high molecular weight immunophilins (IMMs). Albeit many aspects of the molecular mechanism of the corticosteroid receptors are not fully elucidated yet, it was not until recently that the first evidences of the functional importance of Hsps and IMMs in the process of adipocyte differentiation have been described. Hsp90 and the high molecular weight IMM FKBP51 modulate GR and MR activity at multiple levels, that is, hormone binding affinity, their subcellular distribution, and the transcriptional status, among other aspects of the NR function. Interestingly, it has recently been described that Hsp90 and FKBP51 also participate in the control of PPARγ`, a key transcription factor in the control of adipogenesis and the maintenance of the adipocyte phenotype. In addition, novel roles have been uncovered for FKBP51 in the organization of the nuclear architecture through its participation in the reorganization of the nuclear lamina and the control of the subnuclear distribution of GR. Thus, the aim of this review is to integrate and discuss the actual understanding of the role of corticosteroid receptors, their chaperones and cochaperones, in the process of adipocyte differentiation.
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皮质类固醇受体及其伴侣和伴侣:它们如何调节脂肪形成?
众所周知,糖皮质激素和矿物皮质激素是控制脂肪形成以及脂肪组织生理不同方面的激素列表的一部分。它们的作用是通过与糖皮质激素和矿皮质激素受体(分别为GR和MR)结合,并与热休克蛋白(Hsps)和高分子量亲免疫蛋白(IMMs)结合而介导的。尽管皮质类固醇受体的分子机制的许多方面尚未完全阐明,但直到最近才首次有证据表明热休克蛋白和imm在脂肪细胞分化过程中的功能重要性。Hsp90和高分子量IMM FKBP51在多个水平上调节GR和MR活性,即激素结合亲和力、亚细胞分布、转录状态等NR功能。有趣的是,最近有研究表明,Hsp90和FKBP51也参与了PPARγ '的控制,PPARγ '是控制脂肪形成和维持脂肪细胞表型的关键转录因子。此外,FKBP51通过参与核层重组和控制GR的亚核分布,在核结构组织中的新作用已经被发现。因此,本文的目的是整合和讨论对皮质类固醇受体及其伴侣和辅伴侣在脂肪细胞分化过程中的作用的实际理解。
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