With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage.
With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage.
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DOI：
10.3390/cells10113121
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发表时间：
2021-11-11
期刊：
影响因子：
6
通讯作者：
Schisler JC
中科院分区：
文献类型：
--
作者：
Altinok S;Sanchez-Hodge R;Stewart M;Smith K;Schisler JC
热休克蛋白（HSPs）是一类分子伴侣蛋白，它调节必需的蛋白质重折叠和分类决定，以维持蛋白质稳态。许多共伴侣蛋白直接相互作用并修饰热休克蛋白的功能，这些相互作用影响蛋白质分类的结果，影响从结构蛋白到细胞信号传导介质的一切。伴侣/共同伴侣机制防止各种压力源，以确保细胞在面对压力时的功能。然而，编码突变、表达变化和伴侣/共伴侣机制的翻译后修饰可以改变细胞的应激反应。重要的是，这些功能障碍似乎导致了许多人类疾病。由于热休克蛋白的巨大功能，治疗靶向性伴侣是一种有吸引力但具有挑战性的方法，可能导致这些治疗的脱靶效应。目前的工作重点是针对共同伴侣开发精确的治疗方法，以治疗由蛋白质质量控制缺陷引起的许多疾病。本文综述了HSP70/HSP90共伴蛋白的研究进展，重点介绍了其在心脏保护、神经保护、癌症和自身免疫性疾病方面的研究进展。我们还讨论了强调靶向共同伴侣的效用和挑战的治疗方法。
Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensure cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, with a concentration on cardioprotection, neuroprotection, cancer, and autoimmune diseases. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.
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