Substrate selection by the proteasome through initiation regions

Protein Sci. 2019 Jul;28(7):1222-1232. doi: 10.1002/pro.3642. Epub 2019 May 23.


Proteins in the cell have to be eliminated once their function is no longer desired or they become damaged. Most regulated protein degradation is achieved by a large enzymatic complex called the proteasome. Many proteasome substrates are targeted for degradation by the covalent attachment of ubiquitin molecules. Ubiquitinated proteins can be bound by the proteasome, but for proteolysis to occur the proteasome needs to find a disordered tail somewhere in the target at which it initiates degradation. The initiation step contributes to the specificity of proteasomal degradation. Here, we review how the proteasome selects initiation sites within its substrates and discuss how the initiation step affects physiological processes.

Keywords: initiation region; proteasome; protein degradation; protein unfolding; ubiquitin.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Proteasome Endopeptidase Complex / metabolism*
  • Substrate Specificity
  • Ubiquitin / metabolism


  • Ubiquitin
  • Proteasome Endopeptidase Complex