ArticleCell research2018
Phosphorylation of glutaminase by PKCε is essential for its enzymatic activity and critically contributes to tumorigenesis.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- c-Jun in neurodegeneration: A key transcriptional regulator with therapeutic implications.Molecular therapy. Nucleic acids · 2026Review
- Glutamine alleviates feed restriction-induced barrier function injury in yak rumen epithelium.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Advances in Metabolic Reprogramming and Immune Regulatory Mechanisms in Lung Cancer.Oncology research · 2026Review
- Glutamine relieves feed restriction-induced ruminal epithelial function damage through histone lysine lactylation in yaks.Journal of animal science and biotechnology · 2025Article
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Fueling Prostate Cancer: The Central Role of Glutamine/Glutamate Metabolic Reprogramming.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- GPM6B inhibits tumor progression by targeting HPGD in lung adenocarcinoma.Molecular medicine reports · 2025Article
- Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells.Cell death & disease · 2024Article
- Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death.Cell insight · 2024Article
- The significant role of amino acid metabolic reprogramming in cancer.Cell communication and signaling : CCS · 2024Review
- TRIM65 promotes renal cell carcinoma through ubiquitination and degradation of BTG3.Cell death & disease · 2024Article
- Phosphorylated SHMT2 Regulates Oncogenesis Through mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Oxygen and Iron Availability Shapes Metabolic Adaptations of Cancer Cells.World journal of oncology · 2024Review
- Amino acid metabolism in tumor biology and therapy.Cell death & disease · 2024Review
- LncRNA-HOTAIRM1 promotes aerobic glycolysis and proliferation in osteosarcoma via the miR-664b-3p/Rheb/mTOR pathway.Cancer science · 2023Article
- Article
- Regulation of tumor metabolism by post translational modifications on metabolic enzymes.Cancer gene therapy · 2023Review
- ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.Cell death & disease · 2022Article
- Tumor metabolic reprogramming in lung cancer progression.Oncology letters · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutamine metabolism plays an important role in cancer development and progression. Glutaminase C (GAC), the first enzyme in glutaminolysis, has emerged as an important target for cancer therapy and many studies have focused on the mechanism of enhanced GAC expression in cancer cells. However, little is known about the post-translational modification of GAC. Here, we report that phosphorylation is a crucial post-translational modification of GAC, which is responsible for the higher glutaminase activity in lung tumor tissues and cancer cells. We identify the key Ser314 phosphorylation site on GAC that is regulated by the NF-κB-PKCε axis. Blocking Ser314 phosphorylation by the S314A mutation in lung cancer cells inhibits the glutaminase activity, triggers genetic reprogramming, and alleviates tumor malignancy. Furthermore, we find that a high level of GAC phosphorylation correlates with poor survival rate of lung cancer patients. These findings highlight a previously unappreciated mechanism for activation of GAC by phosphorylation and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.
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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.