Immunoproteasomes Preserve Protein Homeostasis upon Interferon-Induced Oxidative Stress
Immunoproteasomes Preserve Protein Homeostasis upon Interferon-Induced Oxidative Stress
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DOI：
10.1016/j.cell.2010.07.036
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发表时间：
2010-08-20
期刊：
影响因子：
64.5
通讯作者：
Krueger, Elke
中科院分区：
文献类型：
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作者：
Seifert, Ulrike;Bialy, Lukasz P.;Krueger, Elke
干扰素（IFN）诱导的免疫蛋白酶体（i-蛋白酶体）与改善的主要组织相容性复合体（MHC）I类抗原的加工有关。在这里，我们表明，i-蛋白酶体的功能，以保护细胞活力的条件下，干扰素诱导的氧化应激。IFN触发活性氧物质的产生，其诱导蛋白质氧化和新生氧化剂损伤蛋白质的形成。我们发现，泛素化机制是伴随着上调响应干扰素，功能的目标有缺陷的核糖体产品（DRiPs）的降解由i-蛋白酶体。细胞和鼠炎症模型中的I-蛋白酶体缺陷导致形成侵袭体样诱导结构和对细胞凋亡的敏感性增加。通过i-蛋白酶体的增强的蛋白水解活性有效清除这些聚集体对于在IFN诱导的氧化应激后保持细胞活力是重要的。我们的研究结果表明，而不是有一个特定的作用，在生产I类抗原，i-蛋白酶体增加抗原呈递的肽供应的一部分，更一般的作用，在维持蛋白质稳态。
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.