Cited by 318Immune Response and Inflammationinterferon and immune responsesNF-κB Signaling Pathways

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The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon

Wang, Chen, Chen, Taoyong, Zhang, Jia, Yang, Mingjin, Li, Nan, Xu, Xiongfei, Cao, Xuetao·2009·Nature Immunology

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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-beta production in Toll-like receptor-triggered macrophages by suppressing adaptor MyD88-dependent activation of transcription factors NF-kappaB 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.

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Authors: Wang, C., Chen, T., Zhang, J., Yang, M., Li, N., Xu, X., & Cao, X.
Affiliations: Second Military Medical University (CN)
Corresponding author: Cao, Xuetao
ORCID: Wang, Chen
Chen, Taoyong
Zhang, Jia
Yang, Mingjin
Li, Nan
Xu, Xiongfei
Cao, Xuetao
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2009-05-31
Volume: 10
Issue: 7
Pages: 744-752
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.1742
OpenAlex: W2077995361
Cited by: 317
References: 46
Citations by year: 2026: 10 · 2025: 10 · 2024: 19 · 2023: 13 · 2022: 27 · 2021: 14 · 2020: 35 · 2019: 14 · 2018: 21 · 2017: 11 · 2016: 26 · 2015: 18 · 2014: 22 · 2013: 19 · 2012: 14
FWCI: 8.34
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: Nrdp1, E3 ubiquitin ligase, Toll-like receptor signaling, type I interferon, interferon-beta, IRF3, NF-κB, AP-1, macrophages, polyubiquitination, vesicular stomatitis virus, endotoxic shock, innate immunity
MeSH terms: Animals, Carrier Proteins, Cell Line, Cells, Cultured, Female, Humans, Interferon Type I, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Protein Binding, Immunoblotting, Protein Serine-Threonine Kinases, Macrophages, Peritoneal, Vesiculovirus, Rhabdoviridae Infections, Sepsis, Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin-Protein Ligases, Toll-Like Receptors, Mice, Myeloid Differentiation Factor 88, Host-Pathogen Interactions

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The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon

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