The heat shock protein 90 (HSP90) chaperone recruits protein kinase clients via cell division cycle 37 (CDC37). Polier et al. have found that CDC37 can directly prevent binding of ATP to kinases and so may affect kinase activity. Interestingly, the ATP-competitive kinase inhibitors vemurafenib (a BRAF inhibitor) and lapatinib (an ERBB2 and epidermal growth factor receptor inhibitor) block the binding of CDC37 to the oncogenic kinases BRAF and ERBB2, thus preventing them from accessing HSP90. As this leads to kinase degradation, it could account for some of the therapeutic effects of these inhibitors.
ORIGINAL RESEARCH PAPER
Polier, S. et al. ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system. Nature Chem. Biol. 17 Mar 2013 (doi:10.1038/nchembio.1212)
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Seton-Rogers, S. An alternative explanation. Nat Rev Cancer 13, 295 (2013). https://doi.org/10.1038/nrc3523
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DOI: https://doi.org/10.1038/nrc3523
