Control of steroid receptor dynamics and function by genomic actions of the cochaperones p23 and Bag-1L.
Control of steroid receptor dynamics and function by genomic actions of the cochaperones p23 and Bag-1L.
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DOI：
10.1621/nrs.12005
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Cato AC
中科院分区：
文献类型：
--
作者：
Cato L;Neeb A;Brown M;Cato AC
分子伴侣包含一组不相关的蛋白质，这些蛋白质促进其他大分子结构的正确组装和拆卸，而它们本身并不属于这些结构的一部分。它们与一组被称为伴侣蛋白的大而多样的共调节因子相关联，这些共调节因子调节它们的功能和特异性。其中，伴侣和辅伴侣调节包括类固醇受体在内的几种信号分子的活性，这些信号分子在配体结合后与细胞核内的离散核苷酸序列相互作用，以控制各种生理和发育基因的表达。分子伴侣和辅伴侣通常为类固醇受体的配体结合提供正确的构象。虽然这一贡献被广泛接受，但最近的研究报道它们进一步调节类固醇受体在配体结合外的作用。它们被认为有助于受体的周转，受体转运到不同的亚细胞定位，受体在染色质上的再循环，甚至稳定受体的dna结合特性。除了这些与分子伴侣的联合作用外，据报道，伴侣还具有独立于分子伴侣的其他功能。其中一些功能也影响类固醇受体的作用。两个研究充分的例子是协伴侣蛋白p23和Bag-1L，它们已被确定为细胞核中类固醇受体活性的调节剂。了解其调控作用的细节将为控制类固醇受体的作用提供新的治疗机会，而不依赖于分子伴侣的广泛影响。
Molecular chaperones encompass a group of unrelated proteins that facilitate the correct assembly and disassembly of other macromolecular structures, which they themselves do not remain a part of. They associate with a large and diverse set of coregulators termed cochaperones that regulate their function and specificity. Amongst others, chaperones and cochaperones regulate the activity of several signaling molecules including steroid receptors, which upon ligand binding interact with discrete nucleotide sequences within the nucleus to control the expression of diverse physiological and developmental genes. Molecular chaperones and cochaperones are typically known to provide the correct conformation for ligand binding by the steroid receptors. While this contribution is widely accepted, recent studies have reported that they further modulate steroid receptor action outside ligand binding. They are thought to contribute to receptor turnover, transport of the receptor to different subcellular localizations, recycling of the receptor on chromatin and even stabilization of the DNA-binding properties of the receptor. In addition to these combined effects with molecular chaperones, cochaperones are reported to have additional functions that are independent of molecular chaperones. Some of these functions also impact on steroid receptor action. Two well-studied examples are the cochaperones p23 and Bag-1L, which have been identified as modulators of steroid receptor activity in nuclei. Understanding details of their regulatory action will provide new therapeutic opportunities of controlling steroid receptor action independent of the widespread effects of molecular chaperones.