Mahalingam D, Swords R, Carew J S, Nawrocki S T, Bhalla K, Giles F J
Institute for Drug Development, Cancer Research and Therapy Centre at the University of Texas Health Science Centre, San Antonio, TX 78229, USA.
Br J Cancer. 2009 May 19;100(10):1523-9. doi: 10.1038/sj.bjc.6605066. Epub 2009 Apr 28.
Heat-shock proteins (HSPs) are molecular chaperones that regulate protein folding to ensure correct conformation and translocation and to avoid protein aggregation. Heat-shock proteins are increased in many solid tumours and haematological malignancies. Many oncogenic proteins responsible for the transformation of cells to cancerous forms are client proteins of HSP90. Targeting HSP90 with chemical inhibitors would degrade these oncogenic proteins, and thus serve as useful anticancer agents. This review provides an overview of the HSP chaperone machinery and the structure and function of HSP90. We also highlight the key oncogenic proteins that are regulated by HSP90 and describe how inhibition of HSP90 could alter the activity of multiple signalling proteins, receptors and transcriptional factors implicated in carcinogenesis.
热休克蛋白（HSPs）是分子伴侣，可调节蛋白质折叠以确保正确的构象和转运，并避免蛋白质聚集。热休克蛋白在许多实体瘤和血液系统恶性肿瘤中表达增加。许多导致细胞转化为癌性形式的致癌蛋白是HSP90的客户蛋白。用化学抑制剂靶向HSP90会降解这些致癌蛋白，因此可作为有用的抗癌药物。本综述概述了HSP伴侣机制以及HSP90的结构和功能。我们还强调了受HSP90调节的关键致癌蛋白，并描述了抑制HSP90如何改变与致癌作用相关的多种信号蛋白、受体和转录因子的活性。
