Recycling Overdrive

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Science  17 Sep 2010:
Vol. 329, Issue 5998, pp. 1442
DOI: 10.1126/science.329.5998.1442-d
CREDIT: SEIFERT ET AL., CELL 142, 613 (2010)

The degradation of polyubiquitylated proteins by the proteasome is critical for maintaining homeostasis in eukaryotic cells. Ubiquitin is a tag that is attached to proteins that are damaged or need to be destroyed. Proteasomes in cells of the immune system incorporate alternative catalytic subunits, and these immunoproteasomes can also be found in non-immune cells in response to inflammation. Immunoproteasomes exhibit altered enzymatic activity that results in the production of peptides that are particularly well suited for binding to the proteins that present antigenic fragments to cytotoxic T cells. Mice that are deficient in these alternative subunits, however, exhibit only modest changes in antigen presentation, and so the function of immunoproteasomes has remained a mystery. One of the outcomes of inflammation is oxidative stress, which results in the formation of nascent oxidantdamaged proteins. Seifert et al. report that mouse cells up-regulate the ubiquitylation machinery in response to inflammation, targeting oxidant-damaged proteins for degradation by the immunoproteasome. In the absence of immunoproteasomes, harmful aggregates of damaged proteins (green) accumulate—for instance, in the liver. These results suggest that rather than antigen presentation, immunoproteasomes are critical for protecting cells against oxidative damage during bouts of inflammation.

Cell 142, 613 (2010).

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