ArticleThe Journal of experimental medicine2020
Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.
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Who cites it
103 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- Integrative multi-omics reveals CUL4B as a modulator of macrophage pyroptosis and innate defense againstScience advances · 2026Article
- Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1.Research square · 2026Article
- The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling.Biomolecules · 2026Review
- Extracellular vesicles from glucocorticoids-preconditioned synovial mesenchymal stem cells exert antiarthritic effects by downregulating the mRNA m6A modification of NLRP3 in macrophages through miR-212-5p.Bioengineering & translational medicine · 2026Article
- Redox Regulation of the NLRP3 Inflammasome and its Implications for Immunization-related Neuroinflammation.Molecular neurobiology · 2026Review
- Macrophage Gsα promotes NLRP3 stability and its intervention attenuates abdominal aortic aneurysm in male mice.Nature communications · 2026Article
- Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026Review
- Neddylation Targets and Stabilizes NLRP3 to Augment Inflammasome-Mediated Colitis and Mood Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Crohn's disease-related RNF123 prevents NLRP3 inflammasome assembly by catalyzing unanchored K63-linked ubiquitination on NEK7.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endothelial miR-7052 Safeguards Blood-Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A.Molecular neurobiology · 2026Article
- 14-3-3ε-dependent deubiquitination and translocation of NLRP3 activates the inflammasome during sepsis.JCI insight · 2026Article
- Advances in protein ubiquitination modification and immune evasion of breast cancer.Frontiers in cell and developmental biology · 2026Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- The role of NLRP3 inflammasome in necrotizing enterocolitis.Pediatric research · 2026Review
- Pyroptosis in premature ovarian insufficiency: pathogenic mechanisms, pathway crosstalk, and therapeutic strategies.Frontiers in medicine · 2026Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- The enigma of the RING-UIM E3 ligases: its transformative impact on cancer research.Journal of translational medicine · 2025Review
- The E3 ubiquitin ligase MARCH9 alleviates pyroptosis by regulating NLPR3 ubiquitination following myocardial ischemia reperfusion.Cellular and molecular life sciences : CMLS · 2025Article
- USP13 stabilizes NLRP3 to facilitate inflammasome activation by preventing TRIM31-mediated NLRP3 ubiquitination and degradation.Science advances · 2025Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
Abstract
Aberrant NLRP3 inflammasome activation contributes to the development of endotoxemia. The importance of negative regulation of NLRP3 inflammasomes remains poorly understood. Here, we show that the E3 ubiquitin ligase Cbl-b is essential for preventing endotoxemia induced by a sub-lethal dose of LPS via a caspase-11/NLRP3-dependent manner. Further studies show that NLRP3 undergoes both K63- and K48-linked polyubiquitination. Cbl-b binds to the K63-ubiquitin chains attached to the NLRP3 leucine-rich repeat domain (LRR) via its ubiquitin-associated region (UBA) and then targets NLRP3 at K496 for K48-linked ubiquitination and proteasome-mediated degradation. We also identify RNF125 as an additional E3 ubiquitin ligase that initiates K63-linked ubiquitination of the NLRP3 LRR domain. Therefore, NLRP3 is sequentially ubiquitinated by K63- and K48-linked ubiquitination, thus keeping the NLRP3 inflammasomes in check and restraining endotoxemia.
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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.