Evidence for an interaction between ubiquitin-conjugating enzymes and the 26S proteasome

Mol Cell Biol. 2000 Jul;20(13):4691-8. doi: 10.1128/MCB.20.13.4691-4698.2000.


The targeting of proteolytic substrates is accomplished by a family of ubiquitin-conjugating (E2) enzymes and a diverse set of substrate recognition (E3) factors. The ligation of a multiubiquitin chain to a substrate can promote its degradation by the proteasome. However, the mechanism that facilitates the translocation of a substrate to the proteasome in vivo is poorly understood. We have discovered that E2 proteins, including Ubc1, Ubc2, Ubc4, and Ubc5, can interact with the 26S proteasome. Significantly, the interaction between Ubc4 and the proteasome is strongly induced by heat stress, consistent with the requirement for this E2 for efficient stress tolerance. A catalytically inactive derivative of Ubc4 (Ubc4(C86A)), which causes toxicity in yeast cells, can also bind the proteasome. Purified proteasomes can ligate ubiquitin to a test substrate without the addition of exogenous E2 protein, suggesting that the ubiquitylation of some proteolytic substrates might be directly coupled to degradation by the proteasome.

Publication types

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

MeSH terms

  • Binding, Competitive
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Hot Temperature
  • Ligases / genetics
  • Ligases / metabolism*
  • Multienzyme Complexes*
  • Mutation
  • Oligopeptides
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Peptides / genetics
  • Peptides / metabolism
  • Proteasome Endopeptidase Complex*
  • Saccharomyces cerevisiae Proteins*
  • Ubiquitin-Conjugating Enzymes
  • Yeasts / genetics
  • Yeasts / metabolism


  • Fungal Proteins
  • Multienzyme Complexes
  • Oligopeptides
  • Peptides
  • Saccharomyces cerevisiae Proteins
  • FLAG peptide
  • UBC5 protein, S cerevisiae
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC4
  • Peptide Hydrolases
  • PRE1 protein, S cerevisiae
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • Ligases