School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea.
BMB Rep. 2009 Oct 31;42(10):623-30. doi: 10.5483/bmbrep.2009.42.10.623.
Hsp90, an evolutionarily conserved molecular chaperone, is involved in the folding, stabilization, activation, and assembly of a wide range of 'client' proteins, thus playing a central role in many biological processes. Especially, several oncoproteins act as Hsp90 client proteins and tumor cells require higher Hsp90 activity than normal cells to maintain their malignancy. For this reason, Hsp90 has emerged as a promising target for anti-cancer drug development. It is still largely unknown how Hsp90 can recognize structurally unrelated client proteins. However, recent progress in structural studies on Hsp90 and its interaction with various co-chaperones has broadened our knowledge of how the Hsp90 ATPase activity, which is essential for its chaperone function, is regulated and coupled with the conformational changes of Hsp90 dimer. This review focuses on the roles of various Hsp90 co-chaperones in the regulation of the Hsp90 ATPase cycle, as well as in the selection of client proteins. In addition, the current development of Hsp90 inhibitors based on the structural information will be discussed.
热休克蛋白 90（Hsp90）是一种进化上保守的分子伴侣，参与多种“客户”蛋白的折叠、稳定、激活和组装，因此在许多生物学过程中发挥着核心作用。特别是，一些癌蛋白作为 Hsp90 的客户蛋白，肿瘤细胞比正常细胞需要更高的 Hsp90 活性来维持其恶性。出于这个原因，Hsp90 已成为抗癌药物开发的有前途的靶点。目前尚不清楚 Hsp90 如何识别结构上不相关的客户蛋白。然而，最近在 Hsp90 及其与各种共伴侣相互作用的结构研究方面的进展拓宽了我们对 Hsp90 ATP 酶活性如何被调节以及与 Hsp90 二聚体构象变化偶联的认识，Hsp90 ATP 酶活性对其伴侣功能至关重要。本综述重点介绍了各种 Hsp90 共伴侣在调节 Hsp90 ATP 酶循环以及客户蛋白选择中的作用。此外，还将讨论基于结构信息的 Hsp90 抑制剂的最新发展。
