Regulation of Proteasomal Degradation by Modulating Proteasomal Initiation Regions

ACS Chem Biol. 2015 Nov 20;10(11):2537-43. doi: 10.1021/acschembio.5b00554. Epub 2015 Aug 21.


Methods for regulating the concentrations of specific cellular proteins are valuable tools for biomedical studies. Artificial regulation of protein degradation by the proteasome is receiving increasing attention. Efficient proteasomal protein degradation requires a degron with two components: a ubiquitin tag that is recognized by the proteasome and a disordered region at which the proteasome engages the substrate and initiates degradation. Here we show that degradation rates can be regulated by modulating the disordered initiation region by the binding of modifier molecules, in vitro and in vivo. These results suggest that artificial modulation of proteasome initiation is a versatile method for conditionally inhibiting the proteasomal degradation of specific proteins.

Publication types

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

MeSH terms

  • Electrophoresis, Polyacrylamide Gel
  • HEK293 Cells
  • Humans
  • Peptide Initiation Factors / genetics*
  • Peptide Initiation Factors / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Folding
  • Proteolysis*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism


  • Peptide Initiation Factors
  • Saccharomyces cerevisiae Proteins
  • Proteasome Endopeptidase Complex