Article abstract
Nature Immunology 10, 744 - 752 (2009)
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.
Correspondence to: Xuetao Cao1 e-mail: caoxt@public3.sta.net.cn
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