ArticleMolecular cell2016
mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 124 citations in OpenAlex.
- Deficiency of protein kinase Cδ reprograms macrophage immunometabolism to suppress pyroptosis and stabilize atherosclerotic plaques.Experimental & molecular medicine · 2026Article
- O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment.Molecular medicine (Cambridge, Mass.) · 2026Review
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- From omics to AI-mapping the pathogenic pathways in type 2 diabetes.FEBS letters · 2025Review
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer.Oncogene · 2025Article
- Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth.Science advances · 2025Article
- Starvation-induced HBP metabolic reprogramming and STAM2 O-GlcNAcylation facilitate bladder cancer metastasis.Scientific reports · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Radiotherapy elicits immunogenic cell death and metabolic shifts in the tumor microenvironment: implications for immunotherapy.International journal of medical sciences · 2025Review
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Metabolic adaptations in prostate cancer.British journal of cancer · 2024Review
- O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis.EMBO reports · 2024Article
- [Latest Findings on the Role of α-Ketoglutarate in Metabolic Syndrome].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- SUMO modifies GβL and mediates mTOR signaling.The Journal of biological chemistry · 2024Article
- Regulation of protein O-GlcNAcylation by circadian, metabolic, and cellular signals.The Journal of biological chemistry · 2024Review
- Immunosurveillance encounters cancer metabolism.EMBO reports · 2024Review
- Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Highly proliferating cells are particularly dependent on glucose and glutamine for bioenergetics and macromolecule biosynthesis. The signals that respond to nutrient fluctuations to maintain metabolic homeostasis remain poorly understood. Here, we found that mTORC2 is activated by nutrient deprivation due to decreasing glutamine catabolites. We elucidate how mTORC2 modulates a glutamine-requiring biosynthetic pathway, the hexosamine biosynthesis pathway (HBP) via regulation of expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), the rate-limiting enzyme of the HBP. GFAT1 expression is dependent on sufficient amounts of glutaminolysis catabolites particularly α-ketoglutarate, which are generated in an mTORC2-dependent manner. Additionally, mTORC2 is essential for proper expression and nuclear accumulation of the GFAT1 transcriptional regulator, Xbp1s. Thus, while mTORC1 senses amino acid abundance to promote anabolism, mTORC2 responds to declining glutamine catabolites in order to restore metabolic homeostasis. Our findings uncover the role of mTORC2 in metabolic reprogramming and have implications for understanding insulin resistance and tumorigenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.