ArticleMolecular and cellular biology2015
SOCS3 Drives Proteasomal Degradation of TBK1 and Negatively Regulates Antiviral Innate Immunity.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Restricted MHC-II trafficking inbioRxiv : the preprint server for biology · 2026Article
- Fish CDK2 recruits Dtx4 to degrade TBK1 through ubiquitination in the antiviral response.eLife · 2026Article
- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
- LncRNA transcriptome analysis of rainbow trout (Virulence · 2025Article
- HCoV-229E Mpro Suppresses RLR-Mediated Innate Immune Signalling Through Cleavage of NEMO and Through Other Mechanisms.International journal of molecular sciences · 2025Article
- Merkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection.PLoS pathogens · 2024Article
- Hepatocyte nuclear factor 1A suppresses innate immune response by inducing degradation of TBK1 to inhibit steatohepatitis.Genes & diseases · 2023Article
- Kremen2 drives the progression of non-small cell lung cancer by preventing SOCS3-mediated degradation of EGFR.Journal of experimental & clinical cancer research : CR · 2023Article
- ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells.Viruses · 2023Article
- Exfoliative Cytology and Genetic Analysis for a Non-Invasive Approach to the Diagnosis of White Sponge Nevus: Case Series.Bioengineering (Basel, Switzerland) · 2023Article
- Targeting Type I Interferon Induction and Signaling: How Zika Virus Escapes from Host Innate Immunity.International journal of biological sciences · 2023Review
- Zika virus alters centrosome organization to suppress the innate immune response.EMBO reports · 2022Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- Regulation of cGAS/STING signaling and corresponding immune escape strategies of viruses.Frontiers in cellular and infection microbiology · 2022Review
- The Kinase MAP4K1 Inhibits Cytosolic RNA-Induced Antiviral Signaling by Promoting Proteasomal Degradation of TBK1/IKKε.Microbiology spectrum · 2021Article
- Review
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- Article
- The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Leukemia Inhibitory Factor Inhibits Plasmacytoid Dendritic Cell Function and Development.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TANK-binding kinase 1 (TBK1)-mediated induction of type I interferon (IFN) plays a critical role in host antiviral responses and immune homeostasis. The negative regulation of TBK1 activity is largely unknown. We report that suppressor of cytokine signaling 3 (SOCS3) inhibits the IFN-β signaling pathway by promoting proteasomal degradation of TBK1. Overexpression and knockdown experiments indicated that SOCS3 is a negative regulator of IFN regulatory factor 3 (IRF3) phosphorylation and IFN-β transcription. Moreover, SOCS3 directly associates with TBK1, and they colocalize in the cytoplasm. SOCS3 catalyzes K48-linked polyubiquitination of TBK1 at Lys341 and Lys344 and promotes subsequent TBK1 degradation. On the contrary, SOCS3 knockdown markedly increases the abundance of TBK1. Interestingly, both the BOX domain of SOCS3 and Ser172 phosphorylation of TBK1 are indispensable for the processes of ubiquitination and degradation. Ectopic expression of SOCS3 significantly inhibits vesicular stomatitis virus (VSV) and influenza A virus strain A/WSN/33 (WSN)-induced IRF3 phosphorylation and facilitates the replication of WSN virus by detecting the transcription of its viral RNA (vRNA). Knockdown of SOCS3 represses WSN replication. Collectively, these results demonstrate that SOCS3 acts as a negative regulator of IFN-β signal by ubiquitinating and degrading TBK1, shed light on the understanding of antiviral innate immunity, and provide a potential target for developing antiviral agents.
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