Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function
Open accessAbstract
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 α-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 α-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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GLS2 catalyzes the hydrolysis of glutamine to glutamate and ammonia and is encoded by a direct p53 target gene.
“GLS2 catalyzes the hydrolysis of glutamine to glutamate and ammonia and is encoded by a direct p53 target gene.197, 198”
From Census and evaluation of p53 target genes (2017) · cites this paper as [198]
Cites
ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis
D'Autréaux, B., & Toledano, M. B. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2256 · Cited by 3,642 · see citing works
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163 · see citing works
Cancer cell metabolism: warburg and beyond
Hsu, P. P., & Sabatini, D. M. (2008) · Cell · doi:10.1016/j.cell.2008.08.021 · Cited by 2,452 · see citing works
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124 · see citing works
TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H. (2006) · Cell · doi:10.1016/j.cell.2006.05.036 · Cited by 2,019 · see citing works
Definition of a consensus binding site for p53
El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., & Vogelstein, B. (1992) · Nature Genetics · doi:10.1038/ng0492-45 · Cited by 1,985 · see citing works
p53 Regulates Mitochondrial Respiration
Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M. (2006) · Science · doi:10.1126/science.1126863 · Cited by 1,650 · see citing works
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235 · see citing works
Self-citationThe antioxidant function of the p53 tumor suppressor
Sablina, A. A., Budanov, A. V., Ilyinskaya, G. V., Agapova, L. S., Kravchenko, J. E., & Chumakov, P. M. (2005) · Nature Medicine · doi:10.1038/nm1320 · Cited by 1,110 · see citing works
Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD
Budanov, A. V., Sablina, A. A., Feinstein, E., Koonin, E. V., & Chumakov, P. M. (2004) · Science · doi:10.1126/science.1095569 · Cited by 731 · see citing works
The P53 pathway: what questions remain to be explored?
Levine, A. J., Hu, W., & Feng, Z. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401910 · Cited by 654 · see citing works
Self-citationFeng, Z., Hu, W., de Stanchina, E., Teresky, A. K., Jin, S., Lowe, S., & Levine, A. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4149 · Cited by 633 · see citing works
Self-citationp53 regulates maternal reproduction through LIF
Hu, W., Feng, Z., Teresky, A. K., & Levine, A. J. (2007) · Nature · doi:10.1038/nature05993 · Cited by 446 · see citing works
Self-citationBensaad, K., & Vousden, K. H. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.04.004 · Cited by 305 · see citing works
The p53MH algorithm and its application in detecting p53-responsive genes
Hoh, J., Jin, S. V., Parrado, T., Edington, J., Levine, A. J., & Ott, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132268899 · Cited by 295 · see citing works
Self-citationFeng, Z., Hu, W., Teresky, A. K., Hernando, E., Cordon-Cardo, C., & Levine, A. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708043104 · Cited by 264 · see citing works
Self-citationTranscriptional Activation of the Human Glutathione Peroxidase Promoter by p53
Tan, M., Li, S., Swaroop, M., Guan, K., Oberley, L. W., & Sun, Y. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.12061 · Cited by 251 · see citing works
Self-citationIdentification of ALDH4 as a p53-inducible gene and its protective role in cellular stresses
Yoon, K., Nakamura, Y., & Arakawa, H. (2004) · Journal of Human Genetics · doi:10.1007/s10038-003-0122-3 · Cited by 236 · see citing works
Albertoni, M., Shaw, P., Nozaki, M., Godard, S., Tenan, M., Hamou, M., Fairlie, D. W., Breit, S., Paralkar, V., de Tribolet, N., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205610 · Cited by 173 · see citing works
p53 tumor suppressor protein regulates the levels of huntingtin gene expression
Feng, Z., Jin, S. V., Zupnick, A., Hoh, J., de Stanchina, E., Lowe, S. W., Prives, C. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1209021 · Cited by 120 · see citing works
Self-citationSzeliga, M., Obara‐Michlewska, M., Matyja, E., Łazarczyk, M., Lobo, C., Hilgier, W., Alonso, F. J., Márquez, J., & Albrecht, J. (2008) · Glia · doi:10.1002/glia.20825 · Cited by 69 · see citing works
Expression of the scaffolding PDZ protein glutaminase‐interacting protein in mammalian brain
Olalla, L., Gutiérrez, A., Jimenez, A. J., Lopez-Tellez, J. F., Khan, Z. U., Pérez, J., Alonso, F. J., Rosa, V. Y. D. L., Campos-Sandoval, J. A., Segura, J. A., et al. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21505 · Cited by 45 · see citing works
Campos-Sandoval, J. A., de la Oliva, A. R. L., Lobo, C., Segura, J. A., Matés, J. M., Alonso, F. J., & Márquez, J. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.12.002 · Cited by 45 · see citing works
Genomic organization and transcriptional analysis of the human l-glutaminase gene
Pérez‐Gómez, C., Matés, J. M., GÓMEZ-FABRE, P. M., et al. (2003) · Biochemical Journal · doi:10.1042/bj20021445 · Cited by 38 · see citing works
Hu, W., Feng, Z., & Tang, M. (2004) · Biochemistry · doi:10.1021/bi048560o · Cited by 31 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Ferroptosis as a p53-mediated activity during tumour suppression
Jiang, L., Kon, N., Li, T., Wang, S.-J., Su, T., Hibshoosh, H., Baer, R., & Gu, W. (2015) · Nature · doi:10.1038/nature14344 · Cited by 3,398 · see citing works
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427 · see citing works
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · see citing works
“Although recent studies indicate that the tumor suppressor p53 is required for the induction of GLS2 in a human tumor cell line (Hu et al., 2010; Suzuki et al., 2010),”
BackgroundInfluentialThe Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes
Levine, A. J., & Puzio-Kuter, A. M. (2010) · Science · doi:10.1126/science.1193494 · Cited by 1,243 · see citing works
Self-citationP53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080 · see citing works
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007 · see citing works
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence
Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., Baer, R., & Gu, W. (2012) · Cell · doi:10.1016/j.cell.2012.04.026 · Cited by 912 · see citing works
Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation
Wang, J.-B., Erickson, J. W., Fuji, R., Ramachandran, S., Gao, P., Dinavahi, R., Wilson, K. F., Ambrosio, A. L. B., Dias, S. M. G., Dang, C. V., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.08.009 · Cited by 821 · see citing works
Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine
Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651 · see citing works
p53 in ferroptosis regulation: The new weapon for the old guardian
Liu, Y., & Gu, W. (2022) · Cell Death & Differentiation · doi:10.1038/s41418-022-00943-y · Cited by 540 · see citing works
Glutaminolysis as a target for cancer therapy
Jin, L., Alesi, G. N., & Kang, S. (2016) · Oncogene · doi:10.1038/onc.2015.447 · Cited by 459 · see citing works
Tumour-associated mutant p53 drives the Warburg effect
Zhang, C., Liu, J., Liang, Y., Wu, R., Zhao, Y., Hong, X., Lin, M., Yu, H., Liu, L., Levine, A. J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3935 · Cited by 434 · see citing works
Self-citationTargeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis
Xiang, Y., Stine, Z. E., Xia, J., Lu, Y., O’Connor, R. S., Altman, B. J., Hsieh, A. L., Gouw, A. M., Thomas, A. G., Gao, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci75836 · Cited by 409 · see citing works
Jacque, N., Ronchetti, A. M., Larrue, C., Meunier, G., Birsen, R., Willems, L., Saland, E., Decroocq, J., Maciel, T. T., Lambert, M., et al. (2015) · Blood · doi:10.1182/blood-2015-01-621870 · Cited by 387 · see citing works
Cancer metabolism: current perspectives and future directions
Muñoz-Pinedo, C., El Mjiyad, N., & Ricci, J.-E. (2012) · Cell Death & Disease · doi:10.1038/cddis.2011.123 · Cited by 385 · see citing works
Lipid Metabolism and Ferroptosis
Lee, J.-Y., Kim, W. K., Bae, K.-H., Lee, S. C., & Lee, E.-W. (2021) · Biology · doi:10.3390/biology10030184 · Cited by 374 · see citing works
The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway.
Korotchkina, L. G., Leontieva, O. V., Bukreeva, E. I., Demidenko, Z. N., Gudkov, A. V., & Blagosklonny, M. V. (2010) · Aging · doi:10.18632/aging.100160 · Cited by 278 · see citing works
Kung, H.-N., Marks, J. R., & Chi, J.-T. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002229 · Cited by 277 · see citing works
The Role of p53 in Metabolic Regulation
Puzio-Kuter, A. M. (2011) · Genes & Cancer · doi:10.1177/1947601911409738 · Cited by 273 · see citing works
James, E. L., Michalek, R. D., Pitiyage, G. N., de Castro, A. M., Vignola, K. S., Jones, J., Mohney, R. P., Karoly, E. D., Prime, S. S., & Parkinson, E. K. (2015) · Journal of Proteome Research · doi:10.1021/pr501221g · Cited by 231 · see citing works
Sayin, V. I., LeBoeuf, S. E., Singh, S. X., Davidson, S. M., Biancur, D., Guzelhan, B. S., Alvarez, S. W., Wu, W. L., Karakousi, T. R., Zavitsanou, A. M., et al. (2017) · eLife · doi:10.7554/elife.28083 · Cited by 231 · see citing works
Cell cycle arrest is not senescence
Blagosklonny, M. V. (2011) · Aging · doi:10.18632/aging.100281 · Cited by 217 · see citing works
Control of glutamine metabolism by the tumor suppressor Rb
Reynolds, M. R., Lane, A. N., Robertson, B., Kemp, S., Liu, Y., Hill, B. G., Dean, D. C., & Clem, B. F. (2014) · Oncogene · doi:10.1038/onc.2012.635 · Cited by 216 · see citing works
Stressin’ Sestrins take an aging fight
Budanov, A. V., Lee, J. H., & Karin, M. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000097 · Cited by 208 · see citing works
Thangavelu, K., Pan, C. Q., Karlberg, T., Balaji, G., Uttamchandani, M., Suresh, V., Schüler, H., Low, B. C., & Sivaraman, J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116573109 · Cited by 206 · see citing works
Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach
Chen, L., & Cui, H. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160922830 · Cited by 184 · see citing works
Glutamine: pleiotropic roles in tumor growth and stress resistance
Shanware, N. P., Mullen, A. R., DeBerardinis, R. J., & Abraham, R. T. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0731-9 · Cited by 176 · see citing works
One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy
Shuvalov, O., Petukhov, A., Daks, A., Fedorova, O., Vasileva, E., & Barlev, N. A. (2017) · Oncotarget · doi:10.18632/oncotarget.15053 · Cited by 168 · see citing works
A model of the mitochondrial basis of bipolar disorder
Morris, G., Walder, K., McGee, S. L., Dean, O. M., Tye, S. J., Maes, M., & Berk, M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.014 · Cited by 162 · see citing works
The role of tumor suppressor p53 in the antioxidant defense and metabolism
Budanov, A. V. (2014) · Subcellular Biochemistry · doi:10.1007/978-94-017-9211-0_18 · Cited by 157 · see citing works
The B55α Subunit of PP2A Drives a p53-Dependent Metabolic Adaptation to Glutamine Deprivation
Reid, M. A., Wang, W.-I., Rosales, K. R., Welliver, M. X., Pan, M., & Kong, M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.008 · Cited by 154 · see citing works
Glutaminolysis and autophagy in cancer
Villar, V. H., Merhi, F., Djavaheri-Mergny, M., & Durán, R. V. (2015) · Autophagy · doi:10.1080/15548627.2015.1053680 · Cited by 143 · see citing works
Bykov, V. J. N., Zhang, Q., Zhang, M., Ceder, S., Abrahmsen, L., & Wiman, K. G. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00021 · Cited by 137 · see citing works
p53 as a hub in cellular redox regulation and therapeutic target in cancer
Eriksson, S. E., Ceder, S., Bykov, V. J. N., & Wiman, K. G. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz005 · Cited by 123 · see citing works
Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities
Kollareddy, M., Dimitrova, E., Vallabhaneni, K. C., Chan, A., Le, T., Chauhan, K. M., Carrero, Z. I., Ramakrishnan, G., Watabe, K., Haupt, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms8389 · Cited by 127 · see citing works
Oxidative stress and antioxidants in the pathophysiology of malignant melanoma
Obrador, E., Liu-Smith, F., Dellinger, R. W., Salvador, R., Meyskens, F. L., & Estrela, J. M. (2019) · Biological Chemistry · doi:10.1515/hsz-2018-0327 · Cited by 119 · see citing works
Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer
Lukey, M. J., Cluntun, A. A., Katt, W. P., Lin, M.-C. J., Druso, J. E., Ramachandran, S., Erickson, J. W., Le, H. H., Wang, Z.-E., Blank, B., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.076 · Cited by 103 · see citing works
Regulation of Metabolic Activity by p53
Flöter, J., Kaymak, I., & Schulze, A. (2017) · Metabolites · doi:10.3390/metabo7020021 · Cited by 81 · see citing works
Myc promotes glutaminolysis in human neuroblastoma through direct activation of glutaminase 2
Xiao, D., Ren, P., Su, H., Yue, M., Xiu, R., Hu, Y., Liu, H., & Qing, G. (2015) · Oncotarget · doi:10.18632/oncotarget.5821 · Cited by 80 · see citing works
From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition
Young, A. M. H., Chakrabarti, B., Roberts, D., Lai, M.-C., Suckling, J., & Baron-Cohen, S. (2016) · Molecular Autism · doi:10.1186/s13229-016-0068-x · Cited by 76 · see citing works
Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism
He, W., Tao, W., Zhang, F., Jie, Q., He, Y., Zhu, W., Tan, J., Shen, W., Li, L., Yang, Y., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15009 · Cited by 68 · see citing works
Vazquez, A., & Oltvai, Z. N. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019538 · Cited by 70 · see citing works
“This prediction is in agreement with empirical observations indicating the activation of glutaminolysis as another major feature of the Warburg effect [30,31,32,33] and with the result of a recent genome-scale metabolic model of mammalian cell metabolism [24].”
ResultWang, Y.-F., Zhang, W.-L., Li, Z.-X., Liu, Y., Tan, J., Yin, H.-Z., Zhang, Z.-C., Piao, X.-J., Ruan, M.-H., Dai, Z.-H., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01797-1 · Cited by 69 · see citing works
Zhou, Y., Niu, W., Luo, Y., Li, H., Xie, Y., Wang, H., Liu, Y., Fan, S., Li, Z., Xiong, W., et al. (2019) · Cancer Science · doi:10.1111/cas.13928 · Cited by 66 · see citing works
Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective
Missiaen, R., Morales-Rodriguez, F., Eelen, G., & Carmeliet, P. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.01.001 · Cited by 58 · see citing works
CerS6 Is a Novel Transcriptional Target of p53 Protein Activated by Non-genotoxic Stress
Fekry, B., Jeffries, K. A., Esmaeilniakooshkghazi, A., Ogretmen, B., Krupenko, S. A., & Krupenko, N. I. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.716902 · Cited by 59 · see citing works
Wang, S.-J., Yu, G., Jiang, L., Li, T., Lin, Q., Tang, Y., & Gu, W. (2013) · Cell Cycle · doi:10.4161/cc.23597 · Cited by 54 · see citing works
- Authors
- Hu, W., Zhang, C., Wu, R., Sun, Y., Levine, A., & Feng, Z.
- Affiliations
- Rutgers Cancer Institute (US)
- Institute for Advanced Study (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-08
- Volume
- 107
- Issue
- 16
- Pages
- 7455-7460
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2867677
- OpenAlex
- W2038652783
- Cited by
- 862
- References
- 25
- Citations by year
- 2026: 33 · 2025: 56 · 2024: 45 · 2023: 55 · 2022: 53 · 2021: 67 · 2020: 49 · 2019: 47 · 2018: 49 · 2017: 45 · 2016: 50 · 2015: 55 · 2014: 73 · 2013: 63 · 2012: 66
- FWCI
- 18.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA143204, P01CA087497, P01CA87497., CA143204-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- GLS2, p53 target genes, cellular energy metabolism, antioxidant defense, glutamate, alpha-ketoglutarate, mitochondrial respiration, ATP production, reduced glutathione, reactive oxygen species, oxidative stress, hepatocellular carcinoma, tumor suppression
- MeSH terms
- Adenosine Triphosphate, Transaminases, Antioxidants, Gene Expression Regulation, Glutathione, Humans, Hydrogen Peroxide, Ketoglutaric Acids, Mitochondria, Oxygen, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Reactive Oxygen Species, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
