【进展】Nature Immunology：发现具有抑制致炎细胞因子蛋白
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E3 ubiquitin ligases对天然免疫和获得性免疫系统具有重要的作用。在最新一项研究中，第二军医大学曹雪涛院士等人报告了Nrdp1，一种E3 ubiquitin ligases具有抑制致炎细胞因子表达的作用，同时还具有促进β干扰素的表达量。
Nrdp1能直接结合MyD88和TBK1，降解Nrdp，激活促进TBK1泛素化。如敲除Nrdp1能抑制MyD88降解，抑制TBK1激活。Nrdp1转基因小鼠表现出对脂多糖诱导的内毒素休克和水泡性口膜炎病毒具有抵抗力。
这些研究结果表明，Nrdp1同时具有adaptor protein和E3 unibiquitin ligase调节TLR应答的功能。
原始出处：
Nature Immunology 31 May 2009 | doi:10.1038/ni.1742
The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon
Chen Wang1,2, Taoyong Chen1,2, Jia Zhang1, Mingjin Yang1, Nan Li1, Xiongfei Xu1 & Xuetao Cao1
E3 ubiquitin ligases are important in both innate and adaptive immunity. Here we report that Nrdp1, an E3 ubiquitin ligase, inhibited the production of proinflammatory cytokines but increased interferon-production in Toll-like receptor–triggered macrophages by suppressing adaptor MyD88–dependent activation of transcription factors NF-B and AP-1 while promoting activation of the kinase TBK1 and transcription factor IRF3. Nrdp1 directly bound and polyubiquitinated MyD88 and TBK1, which led to degradation of MyD88 and activation of TBK1. Knockdown of Nrdp1 inhibited the degradation of MyD88 and the activation of TBK1 and IRF3. Nrdp1-transgenic mice showed resistance to lipopolysaccharide-induced endotoxin shock and to infection with vesicular stomatitis virus. Our data suggest that Nrdp1 functions as both an adaptor protein and an E3 unbiquitin ligase to regulate TLR responses in different ways.
1 National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
2 These authors contributed equally to this work.
Nrdp1能直接结合MyD88和TBK1，降解Nrdp，激活促进TBK1泛素化。如敲除Nrdp1能抑制MyD88降解，抑制TBK1激活。Nrdp1转基因小鼠表现出对脂多糖诱导的内毒素休克和水泡性口膜炎病毒具有抵抗力。
这些研究结果表明，Nrdp1同时具有adaptor protein和E3 unibiquitin ligase调节TLR应答的功能。
原始出处：
Nature Immunology 31 May 2009 | doi:10.1038/ni.1742
The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon
Chen Wang1,2, Taoyong Chen1,2, Jia Zhang1, Mingjin Yang1, Nan Li1, Xiongfei Xu1 & Xuetao Cao1
E3 ubiquitin ligases are important in both innate and adaptive immunity. Here we report that Nrdp1, an E3 ubiquitin ligase, inhibited the production of proinflammatory cytokines but increased interferon-production in Toll-like receptor–triggered macrophages by suppressing adaptor MyD88–dependent activation of transcription factors NF-B and AP-1 while promoting activation of the kinase TBK1 and transcription factor IRF3. Nrdp1 directly bound and polyubiquitinated MyD88 and TBK1, which led to degradation of MyD88 and activation of TBK1. Knockdown of Nrdp1 inhibited the degradation of MyD88 and the activation of TBK1 and IRF3. Nrdp1-transgenic mice showed resistance to lipopolysaccharide-induced endotoxin shock and to infection with vesicular stomatitis virus. Our data suggest that Nrdp1 functions as both an adaptor protein and an E3 unbiquitin ligase to regulate TLR responses in different ways.
1 National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
2 These authors contributed equally to this work.
