Immunoproteasomes Preserve Protein Homeostasis upon Interferon-Induced Oxidative Stress

被引：452

作者：

Seifert, Ulrike ^{[1
]}

Bialy, Lukasz P. ^{[1
]}

Ebstein, Frederic ^{[1
]}

Bech-Otschir, Dawadschargal ^{[1
]}

Voigt, Antje ^{[2
]}

Schroeter, Friederike ^{[1
]}

Prozorovski, Timour ^{[3
]}

Lange, Nicole ^{[1
]}

Steffen, Janos ^{[1
]}

Rieger, Melanie ^{[1
]}

Kuckelkorn, Ulrike ^{[1
]}

Aktas, Orhan ^{[3
]}

Kloetzel, Peter-M. ^{[1
]}

Krueger, Elke ^{[1
]}

机构：

[1] Charite, Inst Biochem CC2, D-13347 Berlin, Germany

[2] Charite, Med Klin Kardiol & Angiol CC13, D-10117 Berlin, Germany

[3] Univ Dusseldorf, Fac Med, Dept Neurol, D-40225 Dusseldorf, Germany

来源：

CELL | 2010年 / 142卷 / 04期

关键词：

NEWLY SYNTHESIZED PROTEINS; CD8(+) T-CELLS; PROTEASOME SYSTEM; GAMMA-INTERFERON; HEAT-SHOCK; INDUCTION; DEGRADATION; UBIQUITIN; IMMUNITY; PATHWAY;

D O I：

10.1016/j.cell.2010.07.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：613 / 624

页数：12

共 49 条

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