Hsp70 and Hsp90--a Relay Team for Protein Folding

Rev Physiol Biochem Pharmacol. 2004;151:1-44. doi: 10.1007/s10254-003-0021-1. Epub 2004 Jan 23.

Abstract

Molecular chaperones are a functionally defined set of proteins which assist the structure formation of proteins in vivo. Without certain protective mechanisms, such as binding nascent polypeptide chains by molecular chaperones, cellular protein concentrations would lead to misfolding and aggregation. In the mammalian system, the molecular chaperones Hsp70 and Hsp90 are involved in the folding and maturation of key regulatory proteins, like steroid hormone receptors, transcription factors, and kinases, some of which are involved in cancer progression. Hsp70 and Hsp90 form a multichaperone complex, in which both are connected by a third protein called Hop. The connection of and the interplay between the two chaperone machineries is of crucial importance for cell viability. This review provides a detailed view of the Hsp70 and Hsp90 machineries, their cofactors and their mode of regulation. It summarizes the current knowledge in the field, including the ATP-dependent regulation of the Hsp70/Hsp90 multichaperone cycle and elucidates the complex interplay and their synergistic interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Animals
  • Cell Survival
  • Disease Progression
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / physiology*
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / physiology*
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Chaperones / metabolism
  • Protein Binding
  • Protein Folding

Substances

  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • Adenosine Triphosphate