ArticleiScience2020
Hexosamine Pathway Activation Improves Protein Homeostasis through the Integrated Stress Response.
Article in iScience, 2020. 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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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
23 citing papers in PubMed, 35 citations in OpenAlex.
- Cycloheximide-resistant ribosomes reveal adaptive translation dynamics in C. elegans.Genetics · 2026Article
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- The GCN-2/eIF-2α/ATF-4 signaling pathway is involved inVirulence · 2025Article
- Excessive glycosylation drives thoracic aortic aneurysm formation through integrated stress response.European heart journal · 2025Article
- Calorie restriction mimetics against aging and inflammation.Biogerontology · 2025Review
- The role of protein O-GlcNAcylation in diabetic cardiomyopathy.Biochemical Society transactions · 2024Review
- Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.Antioxidants (Basel, Switzerland) · 2024Article
- Muscle-specific lack of Gfpt1 triggers ER stress to alleviate misfolded protein accumulation.Disease models & mechanisms · 2024Article
- Review
- O-GlcNAc regulates the mitochondrial integrated stress response by regulating ATF4.Frontiers in aging neuroscience · 2023Article
- The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction inFrontiers in cell and developmental biology · 2023Article
- Review
- Hexosamine pathway activation improves memory but does not extend lifespan in mice.Aging cell · 2022Article
- ProteinMetabolites · 2022Review
- Logic of the Temporal Compartmentalization of the Hepatic Metabolic Cycle.Physiology (Bethesda, Md.) · 2022Review
- Review
- Article
- ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1.Nature communications · 2022Article
- Slt2 Is Required to Activate ER-Stress-Protective Mechanisms through TORC1 Inhibition and Hexosamine Pathway Activation.Journal of fungi (Basel, Switzerland) · 2022Article
- Interference of ArabidopsisFrontiers in plant science · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the hexosamine pathway (HP) through gain-of-function mutations in its rate-limiting enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) ameliorates proteotoxicity and increases lifespan in Caenorhabditis elegans. Here, we investigate the role of the HP in mammalian protein quality control. In mouse neuronal cells, elevation of HP activity led to phosphorylation of both PERK and eIF2α as well as downstream ATF4 activation, identifying the HP as a modulator of the integrated stress response (ISR). Increasing uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) levels through GFAT1 gain-of-function mutations or supplementation with the precursor GlcNAc reduces aggregation of the polyglutamine (polyQ) protein Ataxin-3. Blocking PERK signaling or autophagy suppresses this effect. In C. elegans, overexpression of gfat-1 likewise activates the ISR. Consistently, co-overexpression of gfat-1 and proteotoxic polyQ peptides in muscles reveals a strong protective cell-autonomous role of the HP. Thus, the HP has a conserved role in improving protein quality control through modulation of the ISR.
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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.