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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-6-27
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pubmed:abstractText |
Tight regulation of NF-?B signaling is essential for innate and adaptive immune responses, yet the molecular mechanisms responsible for its negative regulation are not completely understood. Here, we report that NLRX1, a NOD-like receptor family member, negatively regulates Toll-like receptor-mediated NF-?B activation. NLRX1 interacts with TRAF6 or I?B kinase (IKK) in an activation signal-dependent fashion. Upon LPS stimulation, NLRX1 is rapidly ubiquitinated, disassociates from TRAF6, and then binds to the IKK complex, resulting in inhibition of IKK? and IKK? phosphorylation and NF-?B activation. Knockdown of NLRX1 in various cell types markedly enhances IKK phosphorylation and the production of NF-?B-responsive cytokines after LPS stimulation. We further provide in vivo evidence that NLRX1 knockdown in mice markedly enhances susceptibility to LPS-induced septic shock and plasma IL-6 level. Our study identifies a previously unrecognized role for NLRX1 in the negative regulation of TLR-induced NF-?B activation by dynamically interacting with TRAF6 and the IKK complex.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1097-4180
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pubmed:author |
pubmed-author:ChenZhijian JZJ,
pubmed-author:HongJunJ,
pubmed-author:MAYE LEL,
pubmed-author:MatsuedaSatokoS,
pubmed-author:SongyangZhouZ,
pubmed-author:WangHelen YHY,
pubmed-author:WangQinfuQ,
pubmed-author:WangRong-FuRF,
pubmed-author:XiaXiaojunX,
pubmed-author:YangXiaoangX,
pubmed-author:ZhuLiangL
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
843-53
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pubmed:meshHeading |
pubmed-meshheading:21703539-Animals,
pubmed-meshheading:21703539-Cell Line,
pubmed-meshheading:21703539-Cytokines,
pubmed-meshheading:21703539-Humans,
pubmed-meshheading:21703539-I-kappa B Kinase,
pubmed-meshheading:21703539-Lipopolysaccharides,
pubmed-meshheading:21703539-Mice,
pubmed-meshheading:21703539-Mitochondrial Proteins,
pubmed-meshheading:21703539-NF-kappa B,
pubmed-meshheading:21703539-Phosphorylation,
pubmed-meshheading:21703539-Protein Binding,
pubmed-meshheading:21703539-Signal Transduction,
pubmed-meshheading:21703539-TNF Receptor-Associated Factor 6,
pubmed-meshheading:21703539-Toll-Like Receptors,
pubmed-meshheading:21703539-Ubiquitination
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pubmed:year |
2011
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pubmed:articleTitle |
NLRX1 negatively regulates TLR-induced NF-?B signaling by targeting TRAF6 and IKK.
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pubmed:affiliation |
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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