Endoplasmic reticulum associated protein degradation: a chaperone assisted journey to hell

Biochim Biophys Acta. 2010 Jun;1803(6):694-705. doi: 10.1016/j.bbamcr.2010.02.005. Epub 2010 Feb 25.


Recognition and elimination of misfolded proteins are essential cellular processes. More than thirty percent of the cellular proteins are proteins of the secretory pathway. They fold in the lumen or membrane of the endoplasmic reticulum from where they are sorted to their site of action. The folding process, as well as any refolding after cell stress, depends on chaperone activity. In case proteins are unable to acquire their native conformation, chaperones with different substrate specificity and activity guide them to elimination. For most misfolded proteins of the endoplasmic reticulum this requires retro-translocation to the cytosol and polyubiquitylation of the misfolded protein by an endoplasmic reticulum associated machinery. Thereafter ubiquitylated proteins are guided to the proteasome for degradation. This review summarizes our up to date knowledge of chaperone classes and chaperone function in endoplasmic reticulum associated degradation of protein waste.

Publication types

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

MeSH terms

  • Endoplasmic Reticulum / metabolism*
  • HSP40 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Lectins / chemistry
  • Models, Biological
  • Molecular Chaperones / metabolism*
  • Polysaccharides / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Conformation
  • Protein Denaturation
  • Protein Folding
  • Proteins / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • Substrate Specificity
  • Sulfhydryl Compounds / chemistry


  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Lectins
  • Molecular Chaperones
  • Polysaccharides
  • Proteins
  • Sulfhydryl Compounds
  • Proteasome Endopeptidase Complex