Woodford Mark R, Dunn Diana M, Ciciarelli Joseph G, Beebe Kristin, Neckers Len, Mollapour Mehdi
Department of Urology; Cancer Research Institute; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 E. Adams St., Syracuse, NY 13210, USA.
Curr Top Med Chem. 2016;16(25):2792-804. doi: 10.2174/1568026616666160413141753.
Heat shock protein-90 (Hsp90) is a molecular chaperone critical to the folding, stability and activity of over 200 client proteins including many responsible for tumor initiation, progression and metastasis. Hsp90 chaperone function is linked to its ATPase activity and Hsp90 inhibitors interfere with this activity, thereby making Hsp90 an attractive target for cancer therapy. Also post-translational modification (PTM) and co-chaperone proteins modulate Hsp90 function, providing additional targets for secondary inhibition. Recent reports have shown that pathogens utilize both their own Hsp90 and that of their host for the propagation of infectious elements. In this review we will summarize our current knowledge of Hsp90 structure and function in both the pathogen and the host. We will focus on the role of Hsp90 in viral and parasitic diseases and the potential beneficial application of Hsp90 inhibitors alone and in combination with disease-specific inhibitors.
热休克蛋白90（Hsp90）是一种分子伴侣，对200多种客户蛋白的折叠、稳定性和活性至关重要，其中许多蛋白与肿瘤的起始、进展和转移有关。Hsp90的伴侣功能与其ATP酶活性相关，Hsp90抑制剂会干扰这种活性，因此使Hsp90成为癌症治疗的一个有吸引力的靶点。此外，翻译后修饰（PTM）和共伴侣蛋白可调节Hsp90的功能，为二级抑制提供了额外的靶点。最近的报告表明，病原体利用自身的Hsp90以及宿主的Hsp90来传播感染因子。在这篇综述中，我们将总结目前我们对病原体和宿主中Hsp90结构和功能的认识。我们将重点关注Hsp90在病毒和寄生虫疾病中的作用，以及单独使用Hsp90抑制剂和与疾病特异性抑制剂联合使用的潜在有益应用。
