The unravelling of the ubiquitin system

Nat Rev Mol Cell Biol. 2015 May;16(5):322-4. doi: 10.1038/nrm3982.


Today, many scientific discoveries are made using a top-down experimental approach. The ubiquitin system was discovered using a 'classic' bottom-up approach to tackle the question: 'how are cellular proteins selectively degraded?' A simple proteolytic assay, which used a crude cell-extract, was all that was required to address this question; it was followed by fractionation and reconstitution experiments to decipher the role of the components in this multi-step process. This 'biochemistry at its best' approach, which was published in a periodical that today would not be regarded as highly visible, provided magnificent findings.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Lysosomes / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis*
  • Reticulocytes / metabolism
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligase Complexes / metabolism


  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • Proteasome Endopeptidase Complex