Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress.
Cell, 2010/8/20;142(4):613-24.
Seifert U[1], Bialy LP, Ebstein F, Bech-Otschir D, Voigt A, Schröter F, Prozorovski T, Lange N, Steffen J, Rieger M, Kuckelkorn U, Aktas O, Kloetzel PM, Krüger E
Affiliations
PMID: 20723761DOI: 10.1016/j.cell.2010.07.036
Impact factor: 66.85
Abstract
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; Histocompatibility Antigens Class I; Homeostasis; Humans; Inflammation; Interferons; Mice; Mice, Inbred C57BL; Proteasome Endopeptidase Complex; Proteins; Ubiquitination
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