Deubiquitinating enzymes are IN/(trinsic to proteasome function)

Curr Protein Pept Sci. 2004 Jun;5(3):201-11. doi: 10.2174/1389203043379756.


Covalent conjugation of the ubiquitin tag to cellular proteins plays a central role in a number of processes, the most notable among them being degradation by the 26S proteasome. A fundamental property of this process is that ubiquitination, in contrast to subsequent degradation, is reversible due to a number of deubiquitinating enzymes that mediate the disassembly of ubiquitin-protein conjugates. The uniqueness of ubiquitin as a reversible tag necessitates mechanisms to guarantee its efficiency. Interestingly, some deubiquitinating enzymes are associated with the 26S proteasome itself. We include a brief overview of the key proteasome-associated deubiquitinating enzymes such as Rpn11/POH1, UCH37/Uch2, Ubp6/Usp14 and Doa4/Ubp4. We go on to discuss how these enzymes may contribute to, or possibly counteract, proteolysis by the proteasome. For example, cumulative evidence points to a partitioning of proteasome action between proteolysis and deubiquitination. On the one hand, inhibition of proteolysis promotes deubiquitination, while on the other hand, inhibition of deubiquitination can promote proteolysis. The plethora of deubiquitinating enzymes may serve as proof reading devices altering the equilibrium between these two processes and allowing for reversal of fortune at various stages of the process. To promote degradation over deubiquitination, certain polyubiquitin conformations could be stabilized or protected from deubiquitinating enzymes in order that they can serve as efficient targeting signals leading to the proteasome. We hypothesize that polvubiquitin chains could also serve as "timers": by slowing down chain disassembly, longer chains allow ample time for unfolding and proteolysis of the substrate.

Publication types

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

MeSH terms

  • Animals
  • Carboxypeptidases
  • Carrier Proteins / metabolism*
  • Endopeptidases / metabolism*
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Peptide Hydrolases / metabolism
  • Proteasome Endopeptidase Complex*
  • Protein Processing, Post-Translational / physiology
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin Thiolesterase
  • Ubiquitin-Protein Ligase Complexes / metabolism*


  • Carrier Proteins
  • DOA4 protein, S cerevisiae
  • Endosomal Sorting Complexes Required for Transport
  • RPN11 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • Carboxypeptidases
  • Endopeptidases
  • Peptide Hydrolases
  • UCHL5 protein, human
  • Ubiquitin Thiolesterase
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • UBP6 protein, S cerevisiae