Please use this identifier to cite or link to this item:
https://doi.org/10.1038/ncomms15865
DC Field | Value | |
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dc.title | E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP | |
dc.contributor.author | Bist P. | |
dc.contributor.author | Cheong W.S. | |
dc.contributor.author | Ng A. | |
dc.contributor.author | Dikshit N. | |
dc.contributor.author | Kim B.-H. | |
dc.contributor.author | Pulloor N.K. | |
dc.contributor.author | Khameneh H.J. | |
dc.contributor.author | Hedl M. | |
dc.contributor.author | Shenoy A.R. | |
dc.contributor.author | Balamuralidhar V. | |
dc.contributor.author | Malik N.B.A. | |
dc.contributor.author | Hong M. | |
dc.contributor.author | Neutzner A. | |
dc.contributor.author | Chin K.-C. | |
dc.contributor.author | Kobayashi K.S. | |
dc.contributor.author | Bertoletti A. | |
dc.contributor.author | Mortellaro A. | |
dc.contributor.author | Abraham C. | |
dc.contributor.author | MacMicking J.D. | |
dc.contributor.author | Xavier R.J. | |
dc.contributor.author | Sukumaran B. | |
dc.date.accessioned | 2020-09-06T16:04:57Z | |
dc.date.available | 2020-09-06T16:04:57Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Bist P., Cheong W.S., Ng A., Dikshit N., Kim B.-H., Pulloor N.K., Khameneh H.J., Hedl M., Shenoy A.R., Balamuralidhar V., Malik N.B.A., Hong M., Neutzner A., Chin K.-C., Kobayashi K.S., Bertoletti A., Mortellaro A., Abraham C., MacMicking J.D., Xavier R.J., Sukumaran B. (2017). E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP. Nature Communications 8 : 15865. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms15865 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/174491 | |
dc.description.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-?B) 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-?B, 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. © The Author(s) 2017. | |
dc.publisher | Nature Publishing Group | |
dc.source | Unpaywall 20200831 | |
dc.subject | caspase recruitment domain protein 15 | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | muramyl dipeptide | |
dc.subject | protein | |
dc.subject | protein rip2 | |
dc.subject | protein znrf4 | |
dc.subject | transcription factor RelA | |
dc.subject | ubiquitin protein ligase E3 | |
dc.subject | unclassified drug | |
dc.subject | caspase recruitment domain protein 15 | |
dc.subject | DNA binding protein | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | n acetylmuramylalanyl dextro isoglutamine | |
dc.subject | NOD2 protein, human | |
dc.subject | receptor interacting protein serine threonine kinase 2 | |
dc.subject | RIPK2 protein, human | |
dc.subject | ZNRF4 protein, human | |
dc.subject | Znrf4 protein, mouse | |
dc.subject | bacterial disease | |
dc.subject | biodegradation | |
dc.subject | cell organelle | |
dc.subject | cells and cell components | |
dc.subject | enzyme | |
dc.subject | enzyme activity | |
dc.subject | immune response | |
dc.subject | immunity | |
dc.subject | peptide | |
dc.subject | protein | |
dc.subject | rodent | |
dc.subject | animal experiment | |
dc.subject | Article | |
dc.subject | caspase activation and recruitment domain | |
dc.subject | controlled study | |
dc.subject | cytokine release | |
dc.subject | cytokine response | |
dc.subject | endoplasmic reticulum | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | immunity | |
dc.subject | in vitro study | |
dc.subject | in vivo study | |
dc.subject | monocyte | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | protein degradation | |
dc.subject | protein localization | |
dc.subject | protein protein interaction | |
dc.subject | regulatory mechanism | |
dc.subject | signal transduction | |
dc.subject | ubiquitination | |
dc.subject | animal | |
dc.subject | C57BL mouse | |
dc.subject | drug effect | |
dc.subject | genetics | |
dc.subject | HEK293 cell line | |
dc.subject | immunological tolerance | |
dc.subject | immunology | |
dc.subject | Listeria monocytogenes | |
dc.subject | listeriosis | |
dc.subject | metabolism | |
dc.subject | mutant mouse strain | |
dc.subject | pathogenicity | |
dc.subject | physiology | |
dc.subject | signal transduction | |
dc.subject | Bacteria (microorganisms) | |
dc.subject | Listeria monocytogenes | |
dc.subject | Mus | |
dc.subject | Acetylmuramyl-Alanyl-Isoglutamine | |
dc.subject | Animals | |
dc.subject | DNA-Binding Proteins | |
dc.subject | HEK293 Cells | |
dc.subject | Humans | |
dc.subject | Immune Tolerance | |
dc.subject | Listeria monocytogenes | |
dc.subject | Listeriosis | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Mutant Strains | |
dc.subject | Monocytes | |
dc.subject | NF-kappa B | |
dc.subject | Nod2 Signaling Adaptor Protein | |
dc.subject | Receptor-Interacting Protein Serine-Threonine Kinase 2 | |
dc.subject | Signal Transduction | |
dc.subject | Ubiquitination | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1038/ncomms15865 | |
dc.description.sourcetitle | Nature Communications | |
dc.description.volume | 8 | |
dc.description.page | 15865 | |
Appears in Collections: | Elements Staff Publications |
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