ArticleGenes & development2016
IKKβ promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Modulation of NFκB Signaling by Natural Compounds in Sarcoma and Normal Muscle Models.International journal of molecular sciences · 2026Article
- Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases.Communications biology · 2026Article
- Unraveling the therapeutic landscape of miRNAs in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Prognostic signature and tumor microenvironment infiltration based on amino acid metabolism-related genes and lncRNAs of colorectal cancer.Scientific reports · 2025Article
- NF-κB in inflammation and cancer.Cellular & molecular immunology · 2025Review
- Enhanced Antitumor Activity of Korean Black Soybean Cultivar 'Soman' by Targeting STAT-Mediated Aerobic Glycolysis.Antioxidants (Basel, Switzerland) · 2025Article
- Metabolism in the tumor microenvironment: implications for pathogenesis and therapeutics.Frontiers in immunology · 2025Review
- Targeting cellular adaptive responses to glutaminolysis perturbation for cancer therapy.Molecules and cells · 2024Review
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- NF-κB signaling pathway in tumor microenvironment.Frontiers in immunology · 2024Review
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- The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.Biomedicines · 2022Review
- TubularInternational journal of molecular sciences · 2022Article
- Endogenous glutamine is rate-limiting for anti-CD3 and anti-CD28 induced CD4+ T-cell proliferation and glycolytic activity under hypoxia and normoxia.The Biochemical journal · 2022Article
- IKKActa pharmaceutica Sinica. B · 2022Article
- T Cell Metabolism in Infection.Frontiers in immunology · 2022Review
- Review
- DDIT3 Directs a Dual Mechanism to Balance Glycolysis and Oxidative Phosphorylation during Glutamine Deprivation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Glutamine is an essential nutrient for cancer cell survival and proliferation. Enhanced utilization of glutamine often depletes its local supply, yet how cancer cells adapt to low glutamine conditions is largely unknown. Here, we report that IκB kinase β (IKKβ) is activated upon glutamine deprivation and is required for cell survival independently of NF-κB transcription. We demonstrate that IKKβ directly interacts with and phosphorylates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3 (PFKFB3), a major driver of aerobic glycolysis, at Ser269 upon glutamine deprivation to inhibit its activity, thereby down-regulating aerobic glycolysis when glutamine levels are low. Thus, due to lack of inhibition of PFKFB3, IKKβ-deficient cells exhibit elevated aerobic glycolysis and lactate production, leading to less glucose carbons contributing to tricarboxylic acid (TCA) cycle intermediates and the pentose phosphate pathway, which results in increased glutamine dependence for both TCA cycle intermediates and reactive oxygen species suppression. Therefore, coinhibition of IKKβ and glutamine metabolism results in dramatic synergistic killing of cancer cells both in vitro and in vivo. In all, our results uncover a previously unidentified role of IKKβ in regulating glycolysis, sensing low-glutamine-induced metabolic stress, and promoting cellular adaptation to nutrient availability.
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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.