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Trends Biochem Sci. 2017 Oct;42(10):799-811. doi: 10.1016/j.tibs.2017.07.002. Epub 2017 Aug 4.

How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches.

Author information

1
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
2
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: agard@msg.ucsf.edu.

Abstract

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.

PMID:
28784328
PMCID:
PMC5621984
DOI:
10.1016/j.tibs.2017.07.002
[Indexed for MEDLINE]
Free PMC Article

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