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Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions
Cell Stress and Chaperones ( IF 3.3 ) Pub Date : 2020-10-10 , DOI: 10.1007/s12192-020-01167-0
Marissa E Dean 1 , Jill L Johnson 1, 2
Affiliation  

The Hsp90 molecular chaperone is required for the function of hundreds of different cellular proteins. Hsp90 and a cohort of interacting proteins called cochaperones interact with clients in an ATP-dependent cycle. Cochaperone functions include targeting clients to Hsp90, regulating Hsp90 ATPase activity, and/or promoting Hsp90 conformational changes as it progresses through the cycle. Over the last 20 years, the list of cochaperones identified in human cells has grown from the initial six identified in complex with steroid hormone receptors and protein kinases to about fifty different cochaperones found in Hsp90-client complexes. These cochaperones may be placed into three groups based on shared Hsp90 interaction domains. Available evidence indicates that cochaperones vary in client specificity, abundance, and tissue distribution. Many of the cochaperones have critical roles in regulation of cancer and neurodegeneration. A more limited set of cochaperones have cellular functions that may be limited to tissues such as muscle and testis. It is likely that a small set of cochaperones are part of the core Hsp90 machinery required for the folding of a wide range of clients. The presence of more selective cochaperones may allow greater control of Hsp90 activities across different tissues or during development.



中文翻译:


人类 Hsp90 辅助伴侣:组织特异性表达的观点和具有相似体内功能的辅助伴侣的鉴定



Hsp90 分子伴侣是数百种不同细胞蛋白功能所必需的。 Hsp90 和一组称为辅助伴侣的相互作用蛋白在 ATP 依赖性循环中与客户相互作用。辅助伴侣的功能包括将客户靶向 Hsp90、调节 Hsp90 ATP 酶活性和/或在循环过程中促进 Hsp90 构象变化。在过去的 20 年里,在人类细胞中鉴定的辅助伴侣蛋白列表已从最初在类固醇激素受体和蛋白激酶复合物中鉴定的六种增加到在 Hsp90-客户复合物中发现的约 50 种不同的辅助伴侣蛋白。这些共伴侣可根据共享的 Hsp90 相互作用域分为三组。现有证据表明,辅助伴侣在客户特异性、丰度和组织分布方面存在差异。许多共伴侣在癌症和神经退行性疾病的调节中发挥着关键作用。一组更有限的辅助伴侣具有可能仅限于肌肉和睾丸等组织的细胞功能。一小组共伴侣很可能是折叠多种客户所需的核心 Hsp90 机器的一部分。更具选择性的辅助伴侣的存在可能允许在不同组织或发育过程中更好地控制 Hsp90 活性。

更新日期:2020-10-11
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