ArticleThe Journal of experimental medicine2014
The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed, 238 citations in OpenAlex.
- E3 ubiquitin ligase SYVN1 mediates K63-linked ubiquitination of DDX3X to activate Macrophage NLRP3 Inflammasome.bioRxiv : the preprint server for biology · 2026Article
- Ubiquitination-dependent regulation of ferroptosis in ischemic heart and brain.Redox biology · 2026Review
- A proximity ligation screen identifies SNAT2 as a novel target of the MARCH1 E3 ubiquitin ligase.Biology open · 2026Article
- Pyoderma gangrenosum caused by the molecular uncoupling of OTULIN catalytic activity and LUBAC binding.Nature immunology · 2026Article
- [Regulatory mechanisms of post-translational modifications in inflammasome signaling: a review].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Linear ubiquitin chain assembly complex contributes to NLRP3-mediated pyroptotic cell death.iScience · 2026Article
- TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.Nature communications · 2026Article
- The NF-κB transcription factor RelA directs mucosal-associated invariant T-cell development.Immunology and cell biology · 2026Article
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- Isoforskolin inhibits LUBAC/GSDMD/IL-1β cascades in pulmonary fibrosis.Journal of thoracic disease · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Environmental Stressors and Neuroinflammation: Linking Climate Change to Alzheimer's Disease.Current issues in molecular biology · 2025Review
- Spatiotemporal Regulation of STING Activity by Linear Ubiquitination Governs Antiviral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Innate Immune Sensors and Cell Death-Frontiers Coordinating Homeostasis, Immunity, and Inflammation in Skin.Viruses · 2025Review
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- The NLRP3 inflammasome in urogenital cancers: structure, dual function, and therapeutic potential.Frontiers in oncology · 2025Review
- Regulation of the NLRP3 inflammasome by autophagy and mitophagy.Immunological reviews · 2025Review
- Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation.Journal of hepatology · 2024Review
- LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB.Cell death and differentiation · 2024Article
92 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
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Abstract
Linear ubiquitination is a newly discovered posttranslational modification that is currently restricted to a small number of known protein substrates. The linear ubiquitination assembly complex (LUBAC), consisting of HOIL-1L, HOIP, and Sharpin, has been reported to activate NF-κB-mediated transcription in response to receptor signaling by ligating linear ubiquitin chains to Nemo and Rip1. Despite recent advances, the detailed roles of LUBAC in immune cells remain elusive. We demonstrate a novel HOIL-1L function as an essential regulator of the activation of the NLRP3/ASC inflammasome in primary bone marrow-derived macrophages (BMDMs) independently of NF-κB activation. Mechanistically, HOIL-1L is required for assembly of the NLRP3/ASC inflammasome and the linear ubiquitination of ASC, which we identify as a novel LUBAC substrate. Consequently, we find that HOIL-1L(-/-) mice have reduced IL-1β secretion in response to in vivo NLRP3 stimulation and survive lethal challenge with LPS. Together, these data demonstrate that linear ubiquitination is required for NLRP3 inflammasome activation, defining the molecular events of NLRP3 inflammasome activation and expanding the role of LUBAC as an innate immune regulator. Furthermore, our observation is clinically relevant because patients lacking HOIL-1L expression suffer from pyogenic bacterial immunodeficiency, providing a potential new therapeutic target for enhancing inflammation in immunodeficient patients.
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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.