曹雪涛又发《Nature Immunology》文章

　　

生物通报道，09年上半年连续发表4篇高水平文章的曹雪涛院士近期又发新文章，解析泛素连接酶对干扰素表达的影响，文章The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon发表在Nature Immunology上。

 

E3 ubiquitin ligases对天然免疫和获得性免疫系统具有重要的作用。在本研究中，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。

（生物通 小茜）

生物通推荐原文检索：

Nature Immunology

Published online: 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

 

【Abstract】

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.

 

National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.

These authors contributed equally to this work.