Protein degradation and protection against misfolded or damaged proteins

Nature. 2003 Dec 18;426(6968):895-9. doi: 10.1038/nature02263.


The ultimate mechanism that cells use to ensure the quality of intracellular proteins is the selective destruction of misfolded or damaged polypeptides. In eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S proteasome, prevents the accumulation of non-functional, potentially toxic proteins. This process is of particular importance in protecting cells against harsh conditions (for example, heat shock or oxidative stress) and in a variety of diseases (for example, cystic fibrosis and the major neurodegenerative diseases). A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.

Publication types

  • Review

MeSH terms

  • Humans
  • Peptide Hydrolases / metabolism*
  • Proteasome Endopeptidase Complex*
  • Protein Biosynthesis
  • Protein Denaturation
  • Protein Folding*
  • Protein Processing, Post-Translational
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Ubiquitin / metabolism


  • Proteins
  • Ubiquitin
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease