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Targeting the oncogene and kinome chaperone CDC37

Abstract

CDC37 is a molecular chaperone that physically stabilizes the catalytic domains found in protein kinases and is therefore a wide-spectrum regulator of protein phosphorylation. It is also an overexpressed oncoprotein that mediates carcinogenesis by stabilizing the compromised structures of mutant and/or overexpressed oncogenic kinases. Recent work shows that such dependency of malignant cells on increased CDC37 expression is a vulnerability that can be targeted in cancer by agents that deplete or inhibit CDC37. CDC37 is thus a candidate for broad-spectrum molecular cancer therapy.

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Figure 1: Interaction domains in CDC37.
Figure 2: Effects of CDC37 depletion on anabolic signalling and cell stress pathways.
Figure 3: Contrasting effects of targeting HSP90 and CDC37.

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Acknowledgements

We acknowledge the support of the Department of Radiation Oncology at Beth Israel Deaconess Medical Center. These studies were also supported by National Institutes of Health grants 5RO1CA047407 and 3RO1CA094397 (S.K.C.) and a Howard Hughes Medical Institute Medical Student Research Training Fellowship (P.J.G.). Because of space limitations we were unable to cite many significant studies on CDC37 and HSP90. We apologize to the authors of such studies and refer the readers to excellent publications that cite the literature more inclusively (Refs 1,2,3,5,9,10

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Correspondence to Stuart K. Calderwood.

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DATABASES

National cancer institute

anaplastic large cell lymphoma

hepatocellular carcinoma

multiple myeloma

prostate cancer

FURTHER INFORMATION

Didier Picard's list of CDC37 client kinases

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Gray, P., Prince, T., Cheng, J. et al. Targeting the oncogene and kinome chaperone CDC37. Nat Rev Cancer 8, 491–495 (2008). https://doi.org/10.1038/nrc2420

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