• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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