The Hsp90/Cdc37 chaperone system interacts with and supports 60% of the human kinome. Not only are Hsp90 and Cdc37 generally required for initial folding, but many kinases rely on the Hsp90/Cdc37 throughout their lifetimes. A large fraction of these ‘client’ kinases are key oncoproteins, and their interactions with the Hsp90/Cdc37 machinery are crucial for both their normal and malignant activity. Recently, advances in single-particle cryo-electron microscopy (cryoEM) and biochemical strategies have provided the first key molecular insights into kinase–chaperone interactions. The surprising results suggest a re-evaluation of the role of chaperones in the kinase lifecycle, and suggest that such interactions potentially allow kinases to more rapidly respond to key signals while simultaneously protecting unstable kinases from degradation and suppressing unwanted basal activity.

Hsp90/Cdc37 伴侣系统与 60% 的人类激酶组相互作用并为其提供支持。不仅初始折叠通常需要 Hsp90 和 Cdc37，而且许多激酶在其整个生命周期中都依赖于 Hsp90/Cdc37。这些“客户”激酶中的很大一部分是关键癌蛋白，它们与 Hsp90/Cdc37 机制的相互作用对其正常和恶性活动都至关重要。最近，单粒子冷冻电子显微镜 (cryoEM) 和生化策略的进展为激酶-伴侣相互作用提供了第一个关键的分子见解。令人惊讶的结果表明需要重新评估分子伴侣在激酶生命周期中的作用，