ArticleMolecular cell2018
MLKL Requires the Inositol Phosphate Code to Execute Necroptosis.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 173 citations in OpenAlex.
- Phosphoinositides and inositol phosphates as molecular glues.FEBS letters · 2026Review
- IPMK at the crossroads of cellular signaling in health and disease.FEBS letters · 2026Review
- A non-classical necroptosis pathway mediated by caspases.Cell communication and signaling : CCS · 2026Article
- Tollip antagonizes ESCRT-III-mediated plasma membrane repair and cell recovery.Cell regeneration (London, England) · 2026Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
- NPM3 functions as a lactyltransferase to promote necroptosis in male diabetic cardiomyopathy mice models via FASN transcription modulation.Nature communications · 2026Article
- Copper homeostasis and cuproptosis in tumor biology: mechanistic insights and clinical perspectives.Frontiers in immunology · 2026Review
- Natural products reshape osteosarcoma cell fate: promoting cell death.Frontiers in pharmacology · 2026Review
- A minimum catalytic unit for synthesis of InsP6 and 5-PP-InsP5 in Arabidopsis.The Biochemical journal · 2025Article
- Structural Rationalization of IPMK Inhibitor Potency.Journal of medicinal chemistry · 2025Article
- Apomorphine is a novel necroptosis inhibitor targeting mixed lineage kinase domain-like protein oligomerization.Cell death discovery · 2025Article
- Dovitinib Ameliorates Inflammation-Related Diseases by Inhibiting Necroptosis and Ferroptosis.ACS chemical biology · 2025Article
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- From Obscurity to Prominence: IPMK's Expanding Role in Cellular Signaling, Physiology, and Disease.Biomolecules · 2025Review
- Conservation of heat stress acclimation by the IPK2-type kinases that control the synthesis of the inositol pyrophosphate 4/6-InsP7 in land plants.PLoS genetics · 2025Article
- Design, Synthesis, and Cellular Characterization of a New Class of IPMK Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Harnessing the FGFR2/NF2/YAP signaling-dependent necroptosis to develop an FGFR2/IL-8 dual blockade therapeutic strategy.Nature communications · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Genetic targets related to aging for the treatment of coronary artery disease.BMC medical genomics · 2025Article
- RIPK3 coordinates RHIM domain-dependent antiviral inflammatory transcription in neurons.Science signaling · 2025Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Necroptosis is an important form of lytic cell death triggered by injury and infection, but whether mixed lineage kinase domain-like (MLKL) is sufficient to execute this pathway is unknown. In a genetic selection for human cell mutants defective for MLKL-dependent necroptosis, we identified mutations in IPMK and ITPK1, which encode inositol phosphate (IP) kinases that regulate the IP code of soluble molecules. We show that IP kinases are essential for necroptosis triggered by death receptor activation, herpesvirus infection, or a pro-necrotic MLKL mutant. In IP kinase mutant cells, MLKL failed to oligomerize and localize to membranes despite proper receptor-interacting protein kinase-3 (RIPK3)-dependent phosphorylation. We demonstrate that necroptosis requires IP-specific kinase activity and that a highly phosphorylated product, but not a lowly phosphorylated precursor, potently displaces the MLKL auto-inhibitory brace region. These observations reveal control of MLKL-mediated necroptosis by a metabolite and identify a key molecular mechanism underlying regulated cell death.
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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.