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Cdc37 and protein kinase folding

  • Chapter
Heat Shock Proteins in Cancer

Part of the book series: Heat Shock Proteins ((HESP,volume 2))

Abstract

Cdc37 is a molecular chaperone that collaborates with Hsp90 to fold protein kinases and other clients including transcription factors. Cdc37 function in protein kinase folding is dependent on direct interaction between the chaperone and the N-lobe of the kinase catalytic domain. In addition, Cdc37 can inhibit the ATPase activity of Hsp90 that is thought to promote assembly of the kinase client with both chaperone proteins. Treatment of cells with the Hsp90 inhibitor, geldanamycin, inhibits assembly of Hsp90:kinase compelxes event although it does not promote disassembly of Hsp90:Cdc37 complexes. Cdc37 interaction with its kinase clients is dependent of phosphorylation at its N-terminus by casein kinase II. Cdc37 is highly expressed in cancer cells and tissues and can promote tumorigenesis when overexpressed. This is correlated with increased levels of Cdk4 and Cdk4:cyclin D complexes that promote cell cycle progression. The chapter focuses on structure function relationships between Cdc37, Hsp90 and their kinase clients. The role of Cdc37 in promoting tumorigenesis is also discussed.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078 Oklahoma, USA

    Robert Matts

  2. Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA

    Avrom J. Caplan

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  1. Robert Matts
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  2. Avrom J. Caplan
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Editors and Affiliations

  1. Harvard Medical School, Boston, U.S.A

    Stuart K. Calderwood

  2. Boston University School of Medicine, Boston, U.S.A

    Michael Y. Sherman

  3. National Research Council CONICET, Mendoza, Argentina

    Daniel R. Ciocca

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Matts, R., Caplan, A.J. (2007). Cdc37 and protein kinase folding. In: Calderwood, S.K., Sherman, M.Y., Ciocca, D.R. (eds) Heat Shock Proteins in Cancer. Heat Shock Proteins, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6401-2_16

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