ArticleThe EMBO journal2021
Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- LDH isozymes as targets for cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- α-ketoglutarate accumulation orchestrates immunosuppressive metabolic remodeling to drive cetuximab resistance in metastatic colorectal cancer.Cell death & disease · 2026Article
- AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression.Cell death & disease · 2026Article
- KDM6A deficiency promotes tumor progression and resistance to cabozantinib treatment in clear cell renal cell carcinoma.Scientific reports · 2025Article
- The multifaceted role of RNF213 in oncogenesis: current insights and future research directions.Discover oncology · 2025Review
- MitCOM-based prognostic model identifies GLUD1 as a key suppressor of glioblastoma growth and invasion through regulation of mitochondrial structure and metabolism.Cancer cell international · 2025Article
- Review
- Glutamate dehydrogenase 1-catalytic glutaminolysis feedback activates EGFR/PI3K/AKT pathway and reprograms glioblastoma metabolism.Neuro-oncology · 2025Article
- IDH2 and GLUD1 depletion arrests embryonic development through an H4K20me3 epigenetic barrier in porcine parthenogenetic embryos.Zoological research · 2024Article
- Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death.Cell insight · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Bioinformatics analysis identifies GLUD1 as a prognostic indicator for clear cell renal cell carcinoma.European journal of medical research · 2024Article
- GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis.Discover oncology · 2024Article
- Targeting Alpha-Ketoglutarate Disruption Overcomes Immunoevasion and Improves PD-1 Blockade Immunotherapy in Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- A comparative analysis of fruit fly and human glutamate dehydrogenases inFrontiers in cell and developmental biology · 2023Article
- Polymorphism and expression ofArchives animal breeding · 2023Article
- Glutamate regulates gliosis of BMSCs to promote ENS regeneration through α-KG and H3K9/H3K27 demethylation.Stem cell research & therapy · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mTORC1 pathway plays key roles in regulating various biological processes, including sensing amino acid deprivation and driving expression of ribosomal protein (RP)-coding genes. In this study, we observed that depletion of glutamate dehydrogenase 1 (GDH1), an enzyme that converts glutamate to α-ketoglutarate (αKG), confers resistance to amino acid deprivation on kidney renal clear cell carcinoma (KIRC) cells. Mechanistically, under conditions of adequate nutrition, GDH1 maintains RP gene expression in a manner dependent on its enzymatic activity. Following amino acid deprivation or mTORC1 inhibition, GDH1 translocates from mitochondria to the cytoplasm, where it becomes ubiquitinated and degraded via the E3 ligase RNF213. GDH1 degradation reduces intracellular αKG levels by more than half and decreases the activity of αKG-dependent lysine demethylases (KDMs). Reduced KDM activity in turn leads to increased histone H3 lysine 9 and 27 methylation, further suppressing RP gene expression and preserving nutrition to support cell survival. In summary, our study exemplifies an economical and efficient strategy of solid tumor cells for coping with amino acid deficiency, which might in the future be targeted to block renal carcinoma progression.
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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.