ArticleScience advances2017
Inositol polyphosphate multikinase promotes Toll-like receptor-induced inflammation by stabilizing TRAF6.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- A large meta-analysis identifies genes associated with anterior uveitis.Nature communications · 2023Pooled it
- IPMK at the crossroads of cellular signaling in health and disease.FEBS letters · 2026Review
- Structural insights into the development of inhibitors for inositol phosphate kinases.FEBS letters · 2026Review
- Phosphorus-specific, liquid chromatography inductively coupled plasma mass spectrometry for analysis of inositol phosphate and inositol pyrophosphate metabolism.The Biochemical journal · 2025Article
- From Obscurity to Prominence: IPMK's Expanding Role in Cellular Signaling, Physiology, and Disease.Biomolecules · 2025Review
- Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF.Nucleic acids research · 2025Article
- A non-catalytic role of IPMK is required for PLCγ1 activation in T cell receptor signaling by stabilizing the PLCγ1-Sam68 complex.Cell communication and signaling : CCS · 2024Article
- Arg1 frommBio · 2024Article
- Resveratrol Inhibits circ_0074371-related Pathway to Alleviate Sepsis-induced Acute Kidney Injury.Biochemical genetics · 2024Article
- Time-Restricted Feeding Ameliorates Methionine-Choline Deficient Diet-Induced Steatohepatitis in Mice.International journal of molecular sciences · 2024Article
- Time-restricted feeding ameliorates MCDD-induced steatohepatitis in mice.bioRxiv : the preprint server for biology · 2023Article
- Article
- SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis.The Journal of clinical investigation · 2023Article
- miRNA-Induced Downregulation of IPMK in Macrophages Mediates Lipopolysaccharide-Triggered TLR4 Signaling.Biomolecules · 2023Article
- NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Immunotherapy landscape analyses of necroptosis characteristics for breast cancer patients.Journal of translational medicine · 2022Article
- Article
- Single-Cell Analysis Uncovers Osteoblast Factor Growth Differentiation Factor 10 as Mediator of Vascular Smooth Muscle Cell Phenotypic Modulation Associated with Plaque Rupture in Human Carotid Artery Disease.International journal of molecular sciences · 2022Article
- TRAF6 Suppresses the Development of Pulmonary Fibrosis by Attenuating the Activation of Fibroblasts.Frontiers in pharmacology · 2022Article
- Mogrol Attenuates Osteoclast Formation and Bone Resorption by Inhibiting the TRAF6/MAPK/NF-κB Signaling PathwayFrontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor (TLR) signaling is tightly controlled to protect hosts from microorganisms while simultaneously preventing uncontrolled immune responses. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a critical mediator of TLR signaling, but the precise mechanism of how TRAF6 protein stability is strictly controlled still remains obscure. We show that myeloid-specific deletion of inositol polyphosphate multikinase (IPMK), which has both inositol polyphosphate kinase activities and noncatalytic signaling functions, protects mice against polymicrobial sepsis and lipopolysaccharide-induced systemic inflammation. IPMK depletion in macrophages results in decreased levels of TRAF6 protein, thereby dampening TLR-induced signaling and proinflammatory cytokine production. Mechanistically, the regulatory role of IPMK is independent of its catalytic function, instead reflecting its direct binding to TRAF6. This interaction stabilizes TRAF6 by blocking its K48-linked ubiquitination and subsequent degradation by the proteasome. Thus, these findings identify IPMK as a key determinant of TRAF6 stability and elucidate the physiological function of IPMK in TLR-induced innate immunity.
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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.