ArticleThe Journal of clinical investigation2023
Posttranslational ISGylation of NLRP3 by HERC enzymes facilitates inflammasome activation in models of inflammation.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review.Cell communication and signaling : CCS · 2025Pooled it
- Multi-Proteomic Insights into Lysine Propionylation and Malonylation Remodeling in PRRSV-Infected Porcine Lungs.Veterinary sciences · 2026Article
- Exploiting Ubiquitination: African Swine Fever Virus-Mediated Recruitment of Host E3 Ligases During Viral Infection and Immune Regulation.Pathogens (Basel, Switzerland) · 2026Review
- Integrated IP-MS and Optoproteomics Reveal Dynamic Remodeling of Protein Interaction Networks During NLRP3 Inflammasome Activation.Molecular & cellular proteomics : MCP · 2026Article
- Interferon α-induced HERC6 provokes podocyte dysfunction via mitotic catastrophe in lupus nephritis.Arthritis research & therapy · 2026Article
- Histone demethylase KDM4B epigenetically controls NLRP3 expression to enhance inflammatory responses.EMBO molecular medicine · 2026Article
- Post-translational modifications of NLRP3: to prime or not to prime?Trends in immunology · 2026Review
- The microbiome-EBV axis in carcinogenesis bridges commensal influence and viral oncogenesis.Frontiers in immunology · 2026Review
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury.Research (Washington, D.C.) · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- When ISG15 is involved in inflammation.Frontiers in immunology · 2026Review
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- The simultaneous targeted Inhibition of ISG15 and HMGCR disrupts cancer stemness through metabolic collapse and induces synthetic lethality in pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- Effect of membrane vesicles produced under different pH conditions on the ability ofJournal of bacteriology · 2025Article
- ISG15 modulates inflammatory profiles and ability to activate CD8 + T cells in bone marrow-derived dendritic cells.Cellular and molecular life sciences : CMLS · 2025Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a crucial component of the innate immune system that initiates inflammatory responses. Posttranslational modifications (PTMs) of NLRP3, including ubiquitination and phosphorylation, control inflammasome activation and determine the intensity of inflammation. However, the role of other PTMs in controlling NLRP3 inflammasome activation remains unclear. This study found that TLR priming induced NLRP3 ISGylation (a type of PTM in which ISG15 covalently binds to the target protein) to stabilize the NLRP3 protein. Viral infection, represented by SARS-COV-2 infection, and type I IFNs induced expression of ISG15 and the predominant E3 ISGylation ligases HECT domain- and RCC1-like domain-containing proteins (HERCs; HERC5 in humans and HERC6 in mice). HERCs promoted NLRP3 ISGylation and inhibited K48-linked ubiquitination and proteasomal degradation, resulting in the enhancement of NLRP3 inflammasome activation. Concordantly, Herc6 deficiency ameliorated NLRP3-dependent inflammation as well as hyperinflammation caused by viral infection. The results illustrate the mechanism by which type I IFNs responses control inflammasome activation and viral infection-induced aberrant NLRP3 activation. This work identifies ISGylation as a PTM of NLRP3, revealing a priming target that modulates NLRP3-dependent immunopathology.
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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.