Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress.
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Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. / Seifert, Ulrike; Bialy, Lukasz P; Ebstein, Frédéric; Bech-Otschir, Dawadschargal; Voigt, Antje; Schröter, Friederike; Prozorovski, Timour; Lange, Nicole; Steffen, Janos; Rieger, Melanie; Kuckelkorn, Ulrike; Aktas, Orhan; Kloetzel, Peter-M; Krüger, Elke.
In: CELL, Vol. 142, No. 4, 4, 2010, p. 613-624.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress.
AU - Seifert, Ulrike
AU - Bialy, Lukasz P
AU - Ebstein, Frédéric
AU - Bech-Otschir, Dawadschargal
AU - Voigt, Antje
AU - Schröter, Friederike
AU - Prozorovski, Timour
AU - Lange, Nicole
AU - Steffen, Janos
AU - Rieger, Melanie
AU - Kuckelkorn, Ulrike
AU - Aktas, Orhan
AU - Kloetzel, Peter-M
AU - Krüger, Elke
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 142
SP - 613
EP - 624
JO - CELL
JF - CELL
SN - 0092-8674
IS - 4
M1 - 4
ER -
