Hsp90: chaperoning signal transduction

J Cell Physiol. 2001 Sep;188(3):281-90. doi: 10.1002/jcp.1131.


Hsp90 is an ATP dependent molecular chaperone involved in the folding and activation of an unknown number of substrate proteins. These substrate proteins include protein kinases and transcription factors. Consistent with this task, Hsp90 is an essential protein in all eucaryotes. The interaction of Hsp90 with its substrate proteins involves the transient formation of multiprotein complexes with a set of highly conserved partner proteins. The specific function of each component in the processing of substrates is still unknown. Large ATP-dependent conformational changes of Hsp90 occur during the hydrolysis reaction and these changes are thought to drive the chaperone cycle. Natural inhibitors of the ATPase activity, like geldanamycin and radicicol, block the processing of Hsp90 substrate proteins. As many of these substrates are critical elements in signal transduction, Hsp90 seems to introduce an additional level of regulation.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Amino Acid Motifs / physiology
  • Animals
  • Enzyme Inhibitors / pharmacology
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Phosphotransferases / metabolism
  • Protein Binding / physiology
  • Protein Conformation / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Signal Transduction / physiology*


  • Enzyme Inhibitors
  • HSP90 Heat-Shock Proteins
  • Adenosine Triphosphate
  • Phosphotransferases
  • Protein-Tyrosine Kinases
  • Adenosine Triphosphatases