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The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon
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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“Importantly, parkin-deficient mice and mice expressing a dominant negative form of Nrdp1 are not reported to have significant neurodegenerative disease171819.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [19]
In the citing paper
“The lack of reported neurodegeneration in parkin-deficient and Nrdp1 mutant mice171819 makes it unlikely that this interaction explains our finding of neurodegeneration in Clec16a mutant mice.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [19]
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Self-citation
Metadata
- 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
- Venue
- Nature Immunology
- Published
- 2009-05-31
- Volume
- 10
- Issue
- 7
- Pages
- 744-752
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- 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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