ArticleProceedings of the National Academy of Sciences of the United States of America2010
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 509 papers, 2 of them syntheses that pooled it.
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Who cites it
509 citing papers in PubMed, 2 syntheses or guidelines pooled it, 830 citations in OpenAlex.
- The molecular mechanism of ferroptosis and its role in COPD.Frontiers in medicine · 2022Pooled it
- Ferroptosis in glioma treatment: Current situation, prospects and drug applications.Frontiers in oncology · 2022Pooled it
- Skeletal Muscle MicroRNA Patterns in Response to a Single Bout of Exercise in Females: Biomarkers for Subsequent Training Adaptation?Biomolecules · 2023Trial
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Targeting the mitochondrial thermogenesis pathway for neuroprotection in neonatal hypoxic-ischemic encephalopathy by curcumin.Acta pharmacologica Sinica · 2026Article
- Non-coding RNAs as master regulators of ferroptosis in cancer: mechanisms and clinical implications.Molecular cancer · 2026Review
- Hepatocellular carcinoma's inflammatory secret: ferroptosis as the key.Translational cancer research · 2026Article
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Ferroptosis reshapes the tumor immune microenvironment: molecular mechanisms, immune regulation, and therapeutic synergistic strategies.Frontiers in immunology · 2026Review
- Emerging links between TLR4 signaling and ferroptosis in heart failure.Frontiers in pharmacology · 2026Review
- CRIP1 promotes docetaxel resistance and immune-associated cell death modulation in prostate cancer.Frontiers in pharmacology · 2026Article
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Bridging innate immunity and iron-dependent death: the interplay between cyclic GMP-AMP synthase-stimulator of interferon genes nexus and ferroptosis in cancer and inflammation.Frontiers in cell and developmental biology · 2026Review
- Development and validation of a CAF-related signature for prognosis and therapy response in colorectal cancer: new insights on HSPB1.NPJ precision oncology · 2025Article
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
449 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
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Abstract
Whereas cell cycle arrest, apoptosis, and senescence are traditionally thought of as the major functions of the tumor suppressor p53, recent studies revealed two unique functions for this protein: p53 regulates cellular energy metabolism and antioxidant defense mechanisms. Here, we identify glutaminase 2 (GLS2) as a previously uncharacterized p53 target gene to mediate these two functions of the p53 protein. GLS2 encodes a mitochondrial glutaminase catalyzing the hydrolysis of glutamine to glutamate. p53 increases the GLS2 expression under both nonstressed and stressed conditions. GLS2 regulates cellular energy metabolism by increasing production of glutamate and alpha-ketoglutarate, which in turn results in enhanced mitochondrial respiration and ATP generation. Furthermore, GLS2 regulates antioxidant defense function in cells by increasing reduced glutathione (GSH) levels and decreasing ROS levels, which in turn protects cells from oxidative stress (e.g., H(2)O(2))-induced apoptosis. Consistent with these functions of GLS2, the activation of p53 increases the levels of glutamate and alpha-ketoglutarate, mitochondrial respiration rate, and GSH levels and decreases reactive oxygen species (ROS) levels in cells. Furthermore, GLS2 expression is lost or greatly decreased in hepatocellular carcinomas and the overexpression of GLS2 greatly reduced tumor cell colony formation. These results demonstrated that as a unique p53 target gene, GLS2 is a mediator of p53's role in energy metabolism and antioxidant defense, which can contribute to its role in tumor suppression.
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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.