Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species
Open accessAbstract
We identified a p53 target gene, phosphate-activated mitochondrial glutaminase (GLS2), a key enzyme in conversion of glutamine to glutamate, and thereby a regulator of glutathione (GSH) synthesis and energy production. GLS2 expression is induced in response to DNA damage or oxidative stress in a p53-dependent manner, and p53 associates with the GLS2 promoter. Elevated GLS2 facilitates glutamine metabolism and lowers intracellular reactive oxygen species (ROS) levels, resulting in an overall decrease in DNA oxidation as determined by measurement of 8-OH-dG content in both normal and stressed cells. Further, siRNA down-regulation of either GLS2 or p53 compromises the GSH-dependent antioxidant system and increases intracellular ROS levels. High ROS levels following GLS2 knockdown also coincide with stimulation of p53-induced cell death. We propose that GLS2 control of intracellular ROS levels and the apoptotic response facilitates the ability of p53 to protect cells from accumulation of genomic damage and allows cells to survive after mild and repairable genotoxic stress. Indeed, overexpression of GLS2 reduces the growth of tumor cells and colony formation. Further, compared with normal tissue, GLS2 expression is reduced in liver tumors. Thus, our results provide evidence for a unique metabolic role for p53, linking glutamine metabolism, energy, and ROS homeostasis, which may contribute to p53 tumor suppressor function.
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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 [197]
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · see citing works
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337 · 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
Glutathione and its role in cellular functions
Sies, H. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00177-x · Cited by 1,735 · 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
Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.
Reitzer, L. J., Wice, B. M., & Kennell, D. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30124-2 · Cited by 1,240 · see citing works
The 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
Brick by brick: metabolism and tumor cell growth
DeBerardinis, R. J., Sayed, N., Ditsworth, D., & Thompson, C. B. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.02.003 · Cited by 1,018 · see citing works
Vousden, K. H., & Ryan, K. M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2715 · Cited by 959 · see citing works
Mathupala, S. P., Ko, Y. H., & Pedersen, P. L. (2006) · Oncogene · doi:10.1038/sj.onc.1209603 · Cited by 766 · see citing works
Trounce, I. A., Kim, Y. L., Jun, A. S., & Wallace, D. C. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)64044-0 · Cited by 749 · 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 Tumor Suppressor p53 Down-Regulates Glucose Transporters GLUT1 and GLUT4 Gene Expression
Bar‐Yoseph, F., Armoni, M., & Karnieli, E. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0846 · Cited by 728 · see citing works
Glycolytic Enzymes Can Modulate Cellular Life Span
Kondoh, H., Lleonart, M. E., Gil, J., Wang, J., Degan, P., Peters, G., Martinez, D., Carnero, A., & Beach, D. (2005) · Cancer Research · doi:10.1158/0008-5472.177.65.1 · Cited by 647 · see citing works
Regulation of Glutaminase Activity and Glutamine Metabolism
Curthoys, N. P., & Watford, M. (1995) · Annual Review of Nutrition · doi:10.1146/annurev.nu.15.070195.001025 · Cited by 643 · see citing works
The contribution of endogenous sources of DNA damage to the multiple mutations in cancer
Jackson, A. L., & Loeb, L. A. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00091-4 · Cited by 630 · see citing works
Bourdon, A., Minai, L., Serre, V., Jaïs, J., Sarzi, E., Aubert, S., Chrétien, D., de Lonlay, P., Paquis‐Flucklinger, V., Arakawa, H., et al. (2007) · Nature Genetics · doi:10.1038/ng2040 · Cited by 530 · see citing works
Mitochondrial metabolism of glutamine and glutamate and its physiological significance.
Kovacevic, Z., & McGivan, J. D. (1983) · Physiological Reviews · doi:10.1152/physrev.1983.63.2.547 · Cited by 374 · see citing works
Matés, J. M., Pérez‐Gómez, C., de Castro, I. N., Asenjo, M., & Márquez, J. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00143-1 · Cited by 340 · see citing works
Bensaad, K., & Vousden, K. H. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.04.004 · Cited by 305 · see citing works
p53 and Metabolism: Inside the TIGAR
Green, D. R., & Chipuk, J. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.032 · Cited by 239 · see citing works
Identification 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
Lebedeva, M. A., Eaton, J. S., & Shadel, G. S. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.01.004 · Cited by 184 · see citing works
Glutathione Turnover in Cultured Astrocytes: Studies with [15N]Glutamate
Yudkoff, M., Pleasure, D., Cregar, L., Lin, Z., Nissim, I. B., Stern, J., & Nissim, I. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb08831.x · Cited by 156 · see citing works
p53 regulates mtDNA copy number and mitocheckpoint pathway
Singh, K., Kulawiec, M., & Vanniarajan, A. (2009) · Journal of Carcinogenesis · doi:10.4103/1477-3163.50893 · Cited by 142 · see citing works
Lora, J., Alonso, F. J., Segura, J. A., Lobo, C., Márquez, J., & Matés, J. M. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04370.x · Cited by 134 · see citing works
Co-expression of glutaminase K and L isoenzymes in human tumour cells
Pérez‐Gómez, C., Campos-Sandoval, J. A., Alonso, F. J., SEGURA, J. A., Manzanares, E., RUIZ-SÁNCHEZ, P., GONZÁLEZ, M. E., Márquez, J., & Matés, J. M. (2005) · Biochemical Journal · doi:10.1042/bj20040996 · Cited by 100 · see citing works
Okamura, S., Ng, C. C., Koyama, K., Takei, Y., Arakawa, H., Monden, M., & Nakamura, Y. (1999) · PubMed · Cited by 95 · see citing works
Chen, K., Albano, A., Ho, A., & Keaney, J. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304423200 · Cited by 95 · see citing works
Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase
GÓMEZ-FABRE, P. M., Aledo, J. C., CASTILLO-OLIVARES, A. D., Alonso, F. J., de Castro, I. N., Campos-Sandoval, J. A., & Márquez, J. (2000) · Biochemical Journal · doi:10.1042/bj3450365 · Cited by 93 · see citing works
Ruiz‐Lozano, P., Hixon, M. L., Wagner, M. W., Flores, A. I., Ikawa, S., Baldwin, A. S., Chien, K. R., & Gualberto, A. (1999) · PubMed · Cited by 69 · see citing works
Hepatic glutaminase expression: relationship to kidney‐type glutaminase and to the urea cycle
Watford, M. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.15.8262331 · Cited by 61 · see citing works
Kvamme, E., Nissen‐Meyer, L. S. H., Roberg, B., & Torgner, I. A. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9589-9 · Cited by 23 · see citing works
The effect of glutamine on A549 cells exposed to moderate hyperoxia
Ogunlesi, F. O., Cho, C., & McGrath‐Morrow, S. A. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2003.10.008 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744 · see citing works
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579 · see citing works
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 hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418 · see citing works
Glutamine and cancer: cell biology, physiology, and clinical opportunities
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69600 · Cited by 1,262 · see citing works
The 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
P53 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 p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016 · 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
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Snezhkina, A. V., Kudryavtseva, A. V., Kardymon, O. L., Savvateeva, M. V., Melnikova, N. V., Krasnov, G. S., & Dmitriev, A. A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6175804 · Cited by 934 · see citing works
Targeting mutant p53 for efficient cancer therapy
Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.109 · Cited by 889 · see citing works
Valavanidis, A., Vlachogianni, T., Fiotakis, K., & Loridas, S. (2013) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph10093886 · Cited by 910 · see citing works
Glutaminolysis: A Hallmark of Cancer Metabolism
Yang, L., Venneti, S., & Nagrath, D. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044546 · Cited by 859 · see citing works
Glutamine Metabolism in Cancer: Understanding the Heterogeneity
Cluntun, A. A., Lukey, M. J., Cerione, R. A., & Locasale, J. W. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.01.005 · Cited by 796 · 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
Tardito, S., Oudin, A., Ahmed, S. U., Fack, F., Keunen, O., Zheng, L., Miletic, H., Sakariassen, P. Ø., Weinstock, A., Wagner, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3272 · Cited by 557 · see citing works
Schulte, M. L., Fu, A., Zhao, P., Li, J., Geng, L., Smith, S. T., Kondo, J., Coffey, R. J., Johnson, M. O., Rathmell, J. C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4464 · Cited by 494 · 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
Liu, W., Le, A., Hancock, C., Lane, A. N., Dang, C. V., Fan, T. W.-M., & Phang, J. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203244109 · Cited by 483 · see citing works
Targeted 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
Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer
Hao, Y., Samuels, Y., Li, Q., Krokowski, D., Guan, B.-J., Wang, C., Jin, Z., Dong, B., Cao, B., Feng, X., et al. (2016) · Nature Communications · doi:10.1038/ncomms11971 · Cited by 290 · 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
Blagosklonny, M. V. (2012) · Aging · doi:10.18632/aging.100443 · Cited by 251 · 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
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
Independent origins of neurons and synapses: insights from ctenophores
Moroz, L. L., & Kohn, A. B. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0041 · Cited by 171 · 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
The transcription factor p53: Not a repressor, solely an activator.
Fischer, M., Steiner, L., & Engeland, K. (2014) · Cell Cycle · doi:10.4161/15384101.2014.949083 · Cited by 153 · 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
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
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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
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Song, Y., Lee, W., Lee, Y.-H., Kang, E., Cha, B.-S., & Lee, B.-W. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17010122 · Cited by 98 · see citing works
“In addition, recent studies have reported that cytosolic p53 interferes with mitochondrial integrity and mitophagy [6,7] by inhibiting the removal of damaged mitochondria through an i hibitory interaction with Parkin, thereby inducing itochon rial dysfunction [8,9].”
BackgroundRegulation 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
Wang, 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
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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
Using Machine Learning to Measure Relatedness Between Genes: A Multi-Features Model
Wang, Y., Yang, S., Zhao, J., Du, W., Liang, Y., Wang, C., Zhou, F., Tian, Y., & Ma, Q. (2019) · Scientific Reports · doi:10.1038/s41598-019-40780-7 · Cited by 26 · see citing works
Dynamic Metabolic Response to Adriamycin-Induced Senescence in Breast Cancer Cells
You, R., Dai, J., Zhang, P., Barding, G. A., & Raftery, D. (2018) · Metabolites · doi:10.3390/metabo8040095 · Cited by 24 · see citing works
Functional investigations of p53 acetylation enabled by heterobifunctional molecules
Chen, L.-Y., Singha Roy, S. J., Jadhav, A. M., Wang, W. W., Chen, P.-H., Bishop, T., Erb, M. A., & Parker, C. G. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00438 · Cited by 18 · see citing works
- Authors
- Suzuki, S., Tanaka, T., Poyurovsky, M. V., Nagano, H., Mayama, T., Ohkubo, S., Lokshin, M., Hosokawa, H., Nakayama, T., Suzuki, Y., Sugano, S., Sato, E., Nagao, T., Yokote, K., Tatsuno, I., & Prives, C.
- Affiliations
- Chiba University (JP)
- Columbia University (US)
- Taiho Pharmaceutical (Japan) (JP)
- The University of Tokyo (JP)
- Tokyo Medical University (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-03-29
- Volume
- 107
- Issue
- 16
- Pages
- 7461-7466
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2867754
- OpenAlex
- W2083659501
- Cited by
- 705
- References
- 36
- Citations by year
- 2026: 32 · 2025: 43 · 2024: 47 · 2023: 48 · 2022: 46 · 2021: 54 · 2020: 39 · 2019: 40 · 2018: 33 · 2017: 46 · 2016: 35 · 2015: 46 · 2014: 62 · 2013: 43 · 2012: 51
- FWCI
- 13.49
- 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
- Takeda Science Foundation
- Sumitomo Foundation
- Tokyo Biochemical Research Foundation
- Ministry of Education, Culture, Sports, Science and Technology (#19659121, 21390147, 17016010)
- Japan Diabetes Foundation
- National Institutes of Health (CA87497)
- Japan Society for the Promotion of Science (21390147)
- National Cancer Institute (CA-87497, P01CA087497, R01CA077742, CA77742)
- 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 › Molecular Biology › Redox biology and oxidative stress
- Keywords
- GLS2, phosphate-activated glutaminase, p53, glutamine metabolism, glutamate, glutathione synthesis, reactive oxygen species, DNA damage, oxidative stress, DNA oxidation, p53 target genes, tumor suppressor function, liver tumors, energy metabolism
- MeSH terms
- Animals, Antioxidants, Glutaminase, Glutamine, Glutathione, Humans, Mitochondria, Promoter Regions, Genetic, Tumor Suppressor Protein p53, Apoptosis, Reactive Oxygen Species, Oligonucleotide Array Sequence Analysis, RNA Interference, Mice
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.
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