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Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4.

CDC37, an essential gene in Saccharomyces cerevisiae, interacts genetically with multiple protein kinases and is required for production of Cdc28p/cyclin complexes through an unknown mechanism. We have identified mammalian p50Cdc37 as a protein kinase-targeting subunit of the molecular chaperone Hsp90. Previously, p50 was observed in complexes with pp60v-src and Raf-1, but its identity and function have remained elusive. In mouse fibroblasts, a primary target of Cdc37 is Cdk4. This kinase is activated by D-type cyclins and functions in passage through G1. In insect cells, Cdc37 is sufficient to target Hsp90 to Cdk4 and both in vitro and in vivo, Cdc37/Hsp90 associates preferentially with the fraction of Cdk4 not bound to D-type cyclins. Cdc37 is coexpressed with cyclin Dl in cells undergoing programmed proliferation in vivo, consistent with a positive role in cell cycle progression. Pharmacological inactivation of Cdc37/Hsp90 function decreases the half-life of newly synthesized Cdk4, indicating a role for Cdc37/Hsp90 in Cdk4 stabilization. This study suggests a general role for p50Cdc37 in signaling pathways dependent on intrinsically unstable protein kinases and reveals a previously unrecognized chaperone-dependent step in the production of Cdk4/cyclin D complexes.

Pubmed ID: 8666233


  • Stepanova L
  • Leng X
  • Parker SB
  • Harper JW


Genes & development

Publication Data

June 15, 1996

Associated Grants

  • Agency: NIA NIH HHS, Id: AG-11085
  • Agency: NIGMS NIH HHS, Id: GM54137
  • Agency: NCI NIH HHS, Id: P50 CA58204

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Cycle Proteins
  • Chaperonins
  • Cloning, Molecular
  • Cyclin D
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • Cyclins
  • Cytoplasm
  • Drosophila Proteins
  • Enzyme Stability
  • Fibroblasts
  • Gene Expression Regulation
  • HSP90 Heat-Shock Proteins
  • Humans
  • Mice
  • Molecular Chaperones
  • Molecular Sequence Data
  • Molecular Weight
  • Proto-Oncogene Proteins
  • Saccharomyces cerevisiae Proteins
  • Sequence Homology, Amino Acid