Regulated protein turnover: snapshots of the proteasome in action

Nat Rev Mol Cell Biol. 2014 Feb;15(2):122-33. doi: 10.1038/nrm3741.


The ubiquitin proteasome system (UPS) is the main ATP-dependent protein degradation pathway in the cytosol and nucleus of eukaryotic cells. At its centre is the 26S proteasome, which degrades regulatory proteins and misfolded or damaged proteins. In a major breakthrough, several groups have determined high-resolution structures of the entire 26S proteasome particle in different nucleotide conditions and with and without substrate using cryo-electron microscopy combined with other techniques. These structures provide some surprising insights into the functional mechanism of the proteasome and will give invaluable guidance for genetic and biochemical studies of this key regulatory system.

Publication types

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

MeSH terms

  • Cell Nucleus / genetics
  • Cryoelectron Microscopy
  • Cytosol / chemistry*
  • Cytosol / metabolism
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / genetics*
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteolysis
  • Ubiquitin / genetics*
  • Ubiquitin / metabolism


  • Multiprotein Complexes
  • Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease