Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress.

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
Cell
Date: Aug. 20, 2010
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