Targeting proteins for degradation

Nat Chem Biol. 2009 Nov;5(11):815-22. doi: 10.1038/nchembio.250.

Abstract

Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cell to avoid toxicity. The concentrations of regulatory proteins are adjusted by degradation at the appropriate time. Both foreign and native proteins are digested into small peptides as part of the adaptive immune response. In eukaryotic cells, an ATP-dependent protease called the proteasome is responsible for much of this proteolysis. Proteins are targeted for proteasomal degradation by a two-part degron, which consists of a proteasome binding signal and a degradation initiation site. Here we describe how both components contribute to the specificity of degradation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Physiological Phenomena
  • Ornithine Decarboxylase / chemistry
  • Ornithine Decarboxylase / metabolism
  • Peptide Chain Initiation, Translational
  • Peptide Hydrolases / metabolism
  • Peptides / chemistry
  • Peptides / metabolism
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Folding
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Ubiquitin / chemistry*
  • Ubiquitin / metabolism*
  • Valosin Containing Protein

Substances

  • Bacterial Proteins
  • Cell Cycle Proteins
  • Peptides
  • Proteins
  • Ubiquitin
  • Adenosine Triphosphate
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases
  • Valosin Containing Protein
  • Ornithine Decarboxylase