ArticleNature immunology2016
Control of the innate immune response by the mevalonate pathway.
Article in Nature immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 3 of them syntheses that pooled it.
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Who cites it
111 citing papers in PubMed, 3 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- Mevalonate kinase deficiency: an updated clinical overview and revision of the SHARE recommendations.Frontiers in immunology · 2024Pooled it
- Does the use of statins alter the risk of rheumatoid arthritis? A systematic review and meta-analysis.PloS one · 2024Pooled it
- Mitochondrial Acetyl-CoA Synthetase 3 is Biosignature of Gastric Cancer Progression.Cancer medicine · 2018Pooled it
- Article
- A metabolic amplification strategy for spherical nucleic acid immunogenicity driven by simvastatin-CpG codelivery.Materials today. Bio · 2026Article
- Metabolic masqueraders of paediatric and adult rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Preoperative LDL-C and mortality after cardiac valve surgery: a retrospective cohort study on the mediating role of inflammatory risk.Lipids in health and disease · 2026Article
- Mevalonic acid exerts procoagulant effect by potentiating factor Xa.Natural products and bioprospecting · 2026Article
- MIF-expressing tumor cells mediate immunotherapeutic resistance in esophageal squamous cell carcinoma.Theranostics · 2026Article
- Cold atmospheric plasma is a promising strategy for treating diabetic retinopathy.Journal of translational medicine · 2025Review
- Cholesterol sensing by the SCAP-FAM134B complex regulates ER-phagy and STING innate immunity.Nature cell biology · 2025Article
- Pyrin inflammasome-driven erosive arthritis caused by unprenylated RHO GTPase signaling.EMBO molecular medicine · 2025Article
- Effect of statins on IL-10 signaling and production by chronic lymphocytic leukemia cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Anti-inflammatory effect of fluvastatin on polarized macrophages and its dependence on the mevalonate pathway.Scientific reports · 2025Article
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Identification of a NEK7-related pyroptosis gene signature against pancreatic cancer and evaluation of its potential in tumor microenvironment remodeling via regulating inflammasome complex.Functional & integrative genomics · 2025Article
- Metabolic Reprogramming in Response to Freund's Adjuvants: Insights from Serum Metabolomics.Microorganisms · 2025Article
- Small nucleolar RNA SNORD13H suppresses tumor progression via FBL-dependent 2'-O-methylation in hepatocellular carcinoma.Frontiers in genetics · 2025Article
- Cholesterol sensing and metabolic adaptation in tissue immunity.Trends in immunology · 2024Review
- Trained Immunity and Trained Tolerance: The Case ofInternational journal of molecular sciences · 2024Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 7 institutions in 2 countries.
Funding
Abstract
Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1β that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.
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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.