ArticlePLoS biology2018
Amino acid starvation sensing dampens IL-1β production by activating riboclustering and autophagy.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Roles of the integrated stress response in regulation of inflammatory reactions.Frontiers in immunology · 2026Review
- Traditional medicine meets modern science: Halofuginone's role in combating autoimmune diseases.Journal of natural medicines · 2025Review
- T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology.International journal of molecular sciences · 2022Review
- Deficiency of T-Cell Intracellular Antigen 1 in Murine Embryonic Fibroblasts Is Associated with Changes in Mitochondrial Morphology and Respiration.International journal of molecular sciences · 2021Article
- Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity.European journal of clinical nutrition · 2021Review
- Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity.Nutrition & diabetes · 2021Review
- Amino acid sensing pathway: A major check point in the pathogenesis of obesity and COVID-19.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021Review
- Polyphenolic-Rich Compounds FromFrontiers in pharmacology · 2021Article
- Review
- Stress Granules in the Post-transcriptional Regulation of Immune Cells.Frontiers in cell and developmental biology · 2020Review
- Obesity-Induced Changes in Bone Marrow Homeostasis.Frontiers in endocrinology · 2020Review
- GCN2-Like Kinase Modulates Stress Granule Formation During Nutritional Stress inFrontiers in cellular and infection microbiology · 2020Article
- Reduction of the RNA Binding Protein TIA1 Exacerbates Neuroinflammation in Tauopathy.Frontiers in neuroscience · 2020Article
- Dengue Virus Induced COX-2 Signaling Is Regulated Through Nutrient Sensor GCN2.Frontiers in immunology · 2020Article
- Dietary Intervention Impacts Immune Cell Functions and Dynamics by Inducing Metabolic Rewiring.Frontiers in immunology · 2020Review
- Amino acid starvation enhances vaccine efficacy by augmenting neutralizing antibody production.Science signaling · 2019Article
- Review
- Amino acid response by Halofuginone in Cancer cells triggers autophagy through proteasome degradation of mTOR.Cell communication and signaling : CCS · 2019Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)-dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes-such as stress granules (SGs)-via recruitment of RNA-binding proteins (RBPs) T cell-restricted intracellular antigen-1(TIA-1)/TIA-1-related (TIAR), which are further cleared through induction of autophagy. GCN2 ablation resulted in reduced autophagy and SG formation, which is inversely correlated with IL-1β production. Furthermore, HF diminishes inflammasome activation through suppression of reactive oxygen species (ROS) production. Our study unveils a novel mechanism by which IL-1β is regulated by AAR and further suggests that administration of HF might offer an effective therapeutic intervention against inflammatory diseases.
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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.