Immuno- and constitutive proteasomes do not differ in their abilities to degrade ubiquitinated proteins

Cell. 2013 Feb 28;152(5):1184-94. doi: 10.1016/j.cell.2013.01.037.


Immunoproteasomes are alternative forms of proteasomes that have an enhanced ability to generate antigenic peptides. Recently, Seifert and colleagues reported surprising observations concerning the functions of immunoproteasomes and cellular responses to interferon-γ: (1) that immunoproteasomes degrade ubiquitinated proteins faster than the constitutive proteasomes, (2) that polyubiquitin conjugates accumulate after interferon-γ treatment but then are preferentially degraded by immunoproteasomes, and (3) that immunoproteasome deficiency causes the formation of inclusions and more severe experimental autoimmune encephalomyelitis (EAE). In contrast, we find that polyubiquitin conjugates do not transiently accumulate following IFNγ-treatment and that immunoproteasomes do not prevent the formation of intracellular inclusions or protect against EAE. Furthermore, purified 26S constitutive and immunoproteasomes bind ubiquitin conjugates similarly and degrade them at similar rates. We conclude that, although immunoproteasomes can increase the generation of peptides appropriate for MHC class I presentation, they do not degrade ubiquitinated proteins more efficiently than constitutive particles.

Publication types

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

MeSH terms

  • Animals
  • Antigens
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Fibroblasts / cytology
  • HeLa Cells
  • Humans
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Polyubiquitin / metabolism
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Processing, Post-Translational
  • Proteins / metabolism*
  • Proteolysis*
  • Spleen / cytology*
  • Ubiquitination


  • Antigens
  • Proteins
  • Polyubiquitin
  • Interferon-gamma
  • LMP7 protein
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease