Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress

Cell. 2010 Aug 20;142(4):613-24. doi: 10.1016/j.cell.2010.07.036.


Interferon (IFN)-induced immunoproteasomes (i-proteasomes) have been associated with improved processing of major histocompatibility complex (MHC) class I antigens. Here, we show that i-proteasomes function to protect cell viability under conditions of IFN-induced oxidative stress. IFNs trigger the production of reactive oxygen species, which induce protein oxidation and the formation of nascent, oxidant-damaged proteins. We find that the ubiquitylation machinery is concomitantly upregulated in response to IFNs, functioning to target defective ribosomal products (DRiPs) for degradation by i-proteasomes. i-proteasome-deficiency in cells and in murine inflammation models results in the formation of aggresome-like induced structures and increased sensitivity to apoptosis. Efficient clearance of these aggregates by the enhanced proteolytic activity of the i-proteasome is important for the preservation of cell viability upon IFN-induced oxidative stress. Our findings suggest that rather than having a specific role in the production of class I antigens, i-proteasomes increase the peptide supply for antigen presentation as part of a more general role in the maintenance of protein homeostasis.

MeSH terms

  • Animals
  • Antigen Presentation
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Homeostasis
  • Humans
  • Inflammation / metabolism
  • Interferons / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Proteasome Endopeptidase Complex / immunology*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteins / metabolism*
  • Ubiquitination


  • Histocompatibility Antigens Class I
  • Proteins
  • Interferons
  • Proteasome Endopeptidase Complex

Associated data

  • GEO/GSE21760