ArticleNature communications2017
E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- DUBA sustains the stability of NOD2 and RIPK2 to enhance innate immune responses.Cell death and differentiation · 2025Article
- Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection.Immunity, inflammation and disease · 2025Review
- CRISPR/Cas9-mediated genome editing reveals seven testis-enriched transmembrane glycoproteins dispensable for male fertility in mice.Andrology · 2025Article
- Current advances on RIPK2 and its inhibitors in pathological processes: a comprehensive review.Frontiers in molecular neuroscience · 2025Review
- YOD1 sustains NOD2-mediated protective signaling in colitis by stabilizing RIPK2.EMBO reports · 2024Article
- Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation.Clinical and translational medicine · 2024Article
- RING finger protein 13 protects against nonalcoholic steatohepatitis by targeting STING-relayed signaling pathways.Nature communications · 2023Article
- Vimentin affects inflammation and neutrophil recruitment in airway epithelium during Streptococcus suis serotype 2 infection.Veterinary research · 2023Article
- NOD2 in monocytes negatively regulates macrophage development through TNFalpha.Frontiers in immunology · 2023Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- FromCells · 2022Review
- Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response.The Journal of clinical investigation · 2021Article
- The E3 ubiquitin ligase RNF186 andProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- TRIM22 inhibits endometrial cancer progression through the NOD2/NF‑κB signaling pathway and confers a favorable prognosis.International journal of oncology · 2020Article
- How to Inactivate Human Ubiquitin E3 Ligases by Mutation.Frontiers in cell and developmental biology · 2020Review
- Fatostatin in Combination with Tamoxifen Induces Synergistic Inhibition in ER-Positive Breast Cancer.Drug design, development and therapy · 2020Article
- LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes.Cell reports · 2019Article
- Twist1 and Twist2 Induce Human Macrophage Memory upon Chronic Innate Receptor Treatment by HDAC-Mediated Deacetylation of Cytokine Promoters.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Modulation of the NOD-like receptors NOD1 and NOD2: A chemist's perspective.Bioorganic & medicinal chemistry letters · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
Optimal regulation of the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is essential for controlling bacterial infections and inflammatory disorders. Chronic NOD2 stimulation induces non-responsiveness to restimulation, termed NOD2-induced tolerance. Although the levels of the NOD2 adaptor, RIP2, are reported to regulate both acute and chronic NOD2 signalling, how RIP2 levels are modulated is unclear. Here we show that ZNRF4 induces K48-linked ubiquitination of RIP2 and promotes RIP2 degradation. A fraction of RIP2 localizes to the endoplasmic reticulum (ER), where it interacts with ZNRF4 under either 55 unstimulated and muramyl dipeptide-stimulated conditions. Znrf4 knockdown monocytes have sustained nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, and Znrf4 knockdown mice have reduced NOD2-induced tolerance and more effective control of Listeria monocytogenes infection. Our results thus demonstrate E3-ubiquitin ligase ZNRF4-mediated RIP2 degradation as a negative regulatory mechanism of NOD2-induced NF-κB, cytokine and anti-bacterial responses in vitro and in vivo, and identify a ZNRF4-RIP2 axis of fine-tuning NOD2 signalling to promote protective host immunity.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.