Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity

Future Med Chem. 2013 Jun;5(9):1059-71. doi: 10.4155/fmc.13.88.


Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Cell Cycle Proteins / metabolism
  • Chaperonins / metabolism
  • Cyclophilins / metabolism
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / metabolism*
  • Homeodomain Proteins / metabolism
  • Humans
  • Intramolecular Oxidoreductases / metabolism
  • Molecular Chaperones / metabolism*
  • Phosphorylation
  • Prostaglandin-E Synthases
  • Protein Processing, Post-Translational
  • Tumor Suppressor Proteins / metabolism


  • AHSA1 protein, human
  • CDC37 protein, human
  • Cell Cycle Proteins
  • HOPX protein, human
  • HSP90 Heat-Shock Proteins
  • Homeodomain Proteins
  • Molecular Chaperones
  • Tumor Suppressor Proteins
  • Chaperonins
  • Cyclophilins
  • PPID protein, human
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases