SIRT4 protein suppresses tumor formation in genetic models of Myc-induced B cell lymphoma
Open accessAbstract
Glutamine metabolism plays an essential role for growth and proliferation of many cancer cells by providing metabolites for the maintenance of mitochondrial functions and macromolecular synthesis. Aberrant activation of the transcription factor c-Myc, e.g. caused by t(8;14) chromosomal translocation commonly found in Burkitt lymphoma, is a key driver of cellular glutamine metabolism in many tumors, highlighting the need to identify molecular mechanisms that can suppress glutamine usage in these cancers. Recently, the mitochondrial sirtuin SIRT4 has been reported to function as a tumor suppressor by regulating glutamine metabolism, suggesting that it might have therapeutic potential for treating glutamine-dependent cancers. Here, we report that SIRT4 represses Myc-induced B cell lymphomagenesis via inhibition of mitochondrial glutamine metabolism. We found that SIRT4 overexpression can dampen glutamine utilization even in Myc-driven human Burkitt lymphoma cells and inhibit glutamine-dependent proliferation of these cells. Importantly, SIRT4 overexpression sensitizes Burkitt lymphoma cells to glucose depletion and synergizes with pharmacological glycolysis inhibitors to induce cell death. Moreover, SIRT4 loss in a genetic mouse model of Myc-induced Burkitt lymphoma, Eμ-Myc transgenic mouse, greatly accelerates lymphomagenesis and mortality. Indeed, Eμ-Myc-induced B cell lymphoma cells from SIRT4 null mice exhibit increased glutamine uptake and glutamate dehydrogenase activity. Furthermore, we establish that SIRT4 regulates glutamine metabolism independent of Myc. Together, these results highlight the tumor-suppressive role of SIRT4 in Myc-induced B cell lymphoma and suggest that SIRT4 may be a potential target against Myc-induced and/or glutamine-dependent cancers.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
SIRT4's overall growth-inhibiting effect results in decreased metabolism and sensitization to glucose inhibition rather than a Warburg-type shift.
“SIRT4 might also seem to drive a dependence on glucose via its inhibition of fat oxidation and glutamine catabolism, but its overall growth-inhibiting effect results in decreased metabolism and a sensitization to glucose inhibition rather than a Warburg-type shift (Jeong et al, JBC 2014).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Jeong et al, JBC 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622 · 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
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001 · see citing works
The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
Adams, J. M., Harris, A. W., Pinkert, C. A., Corcoran, L. M., Alexander, W. S., Cory, S., Palmiter, R. D., & Brinster, R. L. (1985) · Nature · doi:10.1038/318533a0 · Cited by 1,778 · see citing works
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770 · see citing works
Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003428107 · Cited by 1,742 · see citing works
Recent progress in the biology and physiology of sirtuins
Finkel, T., Deng, C., & Mostoslavsky, R. (2009) · Nature · doi:10.1038/nature08197 · Cited by 1,484 · see citing works
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295 · see citing works
Self-citationHaigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162 · see citing works
Self-citationGlucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells
Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.009 · Cited by 1,095 · see citing works
Targeting metabolic transformation for cancer therapy
Tennant, D. A., Durán, R. V., & Gottlieb, E. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2817 · Cited by 1,057 · see citing works
MYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities
Dang, C. V., Le, A., & Gao, P. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0889 · Cited by 934 · see citing works
Modelling Myc inhibition as a cancer therapy
Soucek, L., Whitfield, J. R., Martins, C. P., Finch, A. J., Murphy, D. J., Sodir, N. M., Karnezis, A. N., Swigart, L. B., Nasi, S., & Evan, G. I. (2008) · Nature · doi:10.1038/nature07260 · Cited by 822 · 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
Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells
Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R., & Lazebnik, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200703099 · Cited by 690 · 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 mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4
Csibi, A., Fendt, S.-M., Li, C., Poulogiannis, G., Choo, A. Y., Chapski, D. J., Jeong, S. M., Dempsey, J. M., Parkhitko, A., Morrison, T., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.023 · Cited by 586 · see citing works
Self-citationMaschek, G., Savaraj, N., Priebe, W., Braunschweiger, P. G., Hamilton, K., Tidmarsh, G. F., Young, L. R. D., & Lampidis, T. J. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3294 · Cited by 452 · see citing works
Genetic dissection of the miR-17∼92 cluster of microRNAs in Myc-induced B-cell lymphomasPreprint
Mu, P., Han, Y.-C., Betel, D., Yao, E. S., Squatrito, M., Ogrodowski, P., de Stanchina, E., D’Andrea, A., Sander, C., & Ventura, A. (2009) · Genes & Development · doi:10.1101/gad.1872909 · Cited by 449 · see citing works
Jeong, S. M., Xiao, C., Finley, L. W. S., Lahusen, T., Souza, A. L., Pierce, K., Li, Y.-H., Wang, X., Laurent, G., German, N. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.024 · Cited by 445 · see citing works
Self-citationYang, C., Sudderth, J., Dang, T. T., Bachoo, R. G., McDonald, J. G., & DeBerardinis, R. J. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-2266 · Cited by 425 · see citing works
Rethinking the Warburg Effect with Myc Micromanaging Glutamine Metabolism
Dang, C. V. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3556 · Cited by 379 · see citing works
Robinson, M. M., McBryant, S. J., Tsukamoto, T., Rojas, C. J., Ferraris, D. V., Hamilton, S. K., Hansen, J. C., & Curthoys, N. P. (2007) · Biochemical Journal · doi:10.1042/bj20070039 · Cited by 344 · see citing works
Choo, A. Y., Kim, S. G., Heiden, M. G. V., Mahoney, S. J., Vu, H., Yoon, S.-O., Cantley, L. C., & Blenis, J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.007 · Cited by 248 · see citing works
Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis
Michalak, E. M., Jansen, E. S., Happo, L., Cragg, M. S., Tai, L., Smyth, G. K., Strasser, A., Adams, J. M., & Scott, C. L. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2008.195 · Cited by 152 · see citing works
Therapeutic Targeting of Myc-Reprogrammed Cancer Cell MetabolismPreprint
Dang, C. V. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.011296 · Cited by 104 · see citing works
Papaldo, P., Lopez, M., Cortesi, E., Cammilluzzi, E., Antimi, M., Terzoli, E., Lepidini, G., Vici, P., Barone, C. A., Ferretti, G., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.03.034 · Cited by 78 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Vyas, S., Zaganjor, E., & Haigis, M. C. (2016) · Cell · doi:10.1016/j.cell.2016.07.002 · Cited by 1,735 · see citing works
Self-citationThe multifaceted functions of sirtuins in cancer
Chalkiadaki, A., & Guarente, L. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3985 · Cited by 501 · see citing works
Tafani, M., Sansone, L., Limana, F., Arcangeli, T., Santis, E. D., Polese, M., Fini, M., & Russo, M. A. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3907147 · Cited by 371 · see citing works
The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy
Guo, L., Tian, Y., & Zhu, W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.576946 · Cited by 358 · see citing works
SIRT4 is a lysine deacylase that controls leucine metabolism and insulin secretion
Anderson, K. A., Huynh, F. K., Fisher-Wellman, K., Stuart, J. D., Peterson, B. S., Douros, J. D., Wagner, G. R., Thompson, J. W., Madsen, A. S., Green, M. F., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.003 · Cited by 326 · see citing works
Carrico, C., Meyer, J. G., He, W., Gibson, B. W., & Verdin, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.016 · Cited by 331 · see citing works
The Warburg Effect 97 Years after Its Discovery
Pascale, R. M., Calvisi, D. F., Simile, M. M., Feo, C. F., & Feo, F. (2020) · Cancers · doi:10.3390/cancers12102819 · Cited by 304 · see citing works
Sirtuins: guardians of mammalian healthspan
Giblin, W., Skinner, M. E., & Lombard, D. B. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.04.007 · Cited by 280 · see citing works
Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype
Carafa, V., Altucci, L., & Nebbioso, A. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00038 · Cited by 183 · see citing works
The role of mitochondrial sirtuins in health and disease
Osborne, B., Bentley, N. L., Montgomery, M. K., & Turner, N. A. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.197 · Cited by 179 · see citing works
Cassim, S., Vučetić, M., Ždralević, M., & Pouysségur, J. (2020) · Cancers · doi:10.3390/cancers12051119 · Cited by 176 · see citing works
Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer
Kumar, S., & Lombard, D. B. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6213 · Cited by 158 · see citing works
Nowakowski, G. S., & Czuczman, M. S. (2015) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2015.35.e449 · Cited by 150 · see citing works
Emerging Roles for SIRT5 in Metabolism and Cancer
Bringman, L. R., Guo, A. H., Lyssiotis, C. A., & Lombard, D. B. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7264 · Cited by 140 · see citing works
Lang, A., Grether‐Beck, S., Singh, M., Kuck, F., Jakob, S., Kefalas, A., Altinoluk-Hambüchen, S., Graffmann, N., Schneider, M., Lindecke, A., et al. (2016) · Aging · doi:10.18632/aging.100905 · Cited by 138 · see citing works
Fu, L., Dong, Q., He, J., Wang, X., Xing, J., Wang, E.-H., Qiu, X., & Li, Q. (2016) · Oncogene · doi:10.1038/onc.2016.425 · Cited by 135 · see citing works
The Roles of Mitochondrial SIRT4 in Cellular Metabolism
Min, Z., Gao, J., & Yu, Y. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00783 · Cited by 134 · see citing works
Sirtuin‐dependent epigenetic regulation in the maintenance of genome integrity
Bosch‐Presegué, L., & Vaquero, A. (2015) · The FEBS Journal · doi:10.1111/febs.13053 · Cited by 132 · see citing works
Wang, B., Pei, J., Xu, S.-N., Liu, J., & Yu, J.-M. (2024) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-024-02994-0 · Cited by 129 · see citing works
The Current State of NAD+‐Dependent Histone Deacetylases (Sirtuins) as Novel Therapeutic Targets
Schiedel, M., Robaa, D., Rumpf, T., Sippl, W., & Jung, M. (2017) · Medicinal Research Reviews · doi:10.1002/med.21436 · Cited by 122 · see citing works
The roles of sirtuins family in cell metabolism during tumor development
Zhu, S., Dong, Z., Ke, X., Hou, J., Zhao, E., Zhang, K., Wang, F., Yang, L., Xiang, Z., & Cui, H. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.11.003 · Cited by 113 · see citing works
Sirtuins' control of autophagy and mitophagy in cancer
Aventaggiato, M., Vernucci, E., Barreca, F., Russo, M. A., & Tafani, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107748 · Cited by 103 · see citing works
Targeting sirtuins for cancer therapy: epigenetics modifications and beyond
Shen, H., Qi, X., Hu, Y., Wang, Y., Zhang, J., Liu, Z., & Qin, Z. (2024) · Theranostics · doi:10.7150/thno.100667 · Cited by 95 · see citing works
Popay, T. M., Wang, J., Adams, C. M., Howard, G. C., Codreanu, S. G., Sherrod, S. D., MCLEAN, J. A. J., Thomas, L. R., Lorey, S. L., Machida, Y., et al. (2021) · eLife · doi:10.7554/elife.60191 · Cited by 90 · see citing works
Who watches the watchmen? Regulation of the expression and activity of sirtuins
Buler, M., Andersson, U., & Hakkola, J. (2016) · The FASEB Journal · doi:10.1096/fj.201600410rr · Cited by 84 · see citing works
Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer
Tomaselli, D., Steegborn, C., Mai, A., & Rotili, D. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00474 · Cited by 80 · see citing works
Zwaans, B. M. M., & Lombard, D. B. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.016287 · Cited by 81 · see citing works
Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential
George, J., & Ahmad, N. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2733 · Cited by 81 · see citing works
MYC Rules: Leading Glutamine Metabolism toward a Distinct Cancer Cell Phenotype
Tambay, V., Raymond, V., & Bilodeau, M. (2021) · Cancers · doi:10.3390/cancers13174484 · Cited by 82 · see citing works
Dunleavy, K. M., Little, R. F., & Wilson, W. H. (2016) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2016.07.009 · Cited by 80 · see citing works
Betsinger, C. N., & Cristea, I. M. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00086 · Cited by 80 · see citing works
Dysregulated glycolysis as an oncogenic event
Mikawa, T., LLeonart, M. E., Takaori‐Kondo, A., Inagaki, N., Yokode, M., & Kondoh, H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1840-3 · Cited by 80 · see citing works
Sirtuins and Cancer: Role in the Epithelial‐Mesenchymal Transition
Palmirotta, R., Cives, M., Della‐Morte, D., Capuani, B., Lauro, D., Guadagni, F., & Silvestris, F. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3031459 · Cited by 78 · see citing works
Wang, Y., Du, L., Liang, X., Meng, P., Bi, L., Wang, Y., Wang, C., & Tang, B. (2018) · Hepatology · doi:10.1002/hep.30421 · Cited by 77 · see citing works
Zhu, Y., Yan, Y., Principe, D. R., Zou, X., Vassilopoulos, A., & Gius, D. R. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-15 · Cited by 76 · see citing works
Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism
Jeong, S. M., & Haigis, M. C. (2015) · Molecules and Cells · doi:10.14348/molcells.2015.0167 · Cited by 74 · see citing works
Self-citationCosta‐Machado, L. F., & Fernández-Marcos, P. J. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1634953 · Cited by 66 · see citing works
SIRT4 and Its Roles in Energy and Redox Metabolism in Health, Disease and During Exercise
Han, Y., Zhou, S., Coetzee, S., & Chen, A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01006 · Cited by 69 · see citing works
The pleiotropic effects of the glutamate dehydrogenase (GDH) pathway in Saccharomyces cerevisiae
Mara, P., Fragiadakis, G. S., Gkountromichos, F., & Alexandraki, D. (2018) · Microbial Cell Factories · doi:10.1186/s12934-018-1018-4 · Cited by 65 · see citing works
CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4
Wang, L., Zhou, H., Wang, Y., Cui, G., & Di, L.-J. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.587 · Cited by 62 · see citing works
SIRT4 regulates cancer cell survival and growth after stress
Jeong, S. M., Hwang, S., & Seong, R. H. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.01.078 · Cited by 61 · see citing works
Self-citationNatural Products as Modulators of Sirtuins
Karaman, B., Sippl, W., & Ntie‐Kang, F. (2020) · Molecules · doi:10.3390/molecules25143287 · Cited by 59 · see citing works
Huang, G., Cui, F., Yu, F., Lu, H., Zhang, M., Tang, H., & Peng, Z. (2015) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2015.04.013 · Cited by 58 · see citing works
Chen, Z., Lin, J., Feng, S., Chen, X., Huang, H., Wang, C., Yu, Y., He, Y., Han, S., Zheng, L., et al. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s189536 · Cited by 51 · see citing works
Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer
Ni, R., Li, Z., Li, L., Peng, D., Ming, Y., Li, L., & Liu, Y. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1143798 · Cited by 55 · see citing works
Sirtuin-4 (SIRT4), a therapeutic target with oncogenic and tumor-suppressive activity in cancer
Huang, G., & Zhu, G. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s157724 · Cited by 52 · see citing works
Clinical and therapeutic significance of sirtuin-4 expression in colorectal cancer
Huang, G., Cheng, J., Yu, F., Liu, X., Yuan, C., Liu, C., Chen, X.-L., & Peng, Z. (2016) · Oncology Reports · doi:10.3892/or.2016.4685 · Cited by 52 · see citing works
Sun, H., Huang, D., Liu, G., Jian, F., Zhu, J., & Zhang, L. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s156143 · Cited by 51 · see citing works
Targeting aberrant cancer metabolism – The role of sirtuins
Kleszcz, R., Paluszczak, J., & Baer‐Dubowska, W. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.03.021 · Cited by 49 · see citing works
Yu, M., Ozaki, T., Sun, D., Xing, H., Wei, B., An, J., Yang, J., Gao, Y., Liu, S., Kong, C., et al. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01613-y · Cited by 45 · see citing works
Double-hit lymphomas: current paradigms and novel treatment approaches
Dunleavy, K. M. (2014) · Hematology · doi:10.1182/asheducation-2014.1.107 · Cited by 46 · see citing works
Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4
Castex, J., Willmann, D., Kanouni, T., Arrigoni, L., Li, Y., Friedrich, M. E., Schleicher, M., Wöhrle, S., Pearson, M. A., Kraut, N., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.48 · Cited by 46 · see citing works
Chemical and Physiological Features of Mitochondrial Acylation
Ringel, A. E., Tucker, S. A., & Haigis, M. C. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.10.023 · Cited by 40 · see citing works
Self-citationPoly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity
Brady, P. N., Goel, A., & Johnson, M. A. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00038-18 · Cited by 58 · see citing works
The role of mammalian sirtuins in cancer metabolism
Sebastián, C., & Mostoslavsky, R. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.07.008 · Cited by 39 · see citing works
Aggressive B cell Lymphoma: Optimal Therapy for MYC-positive, Double-Hit, and Triple-Hit DLBCL
Dunleavy, K. M. (2015) · Current Treatment Options in Oncology · doi:10.1007/s11864-015-0374-0 · Cited by 37 · see citing works
Targeting MYC Dependence by Metabolic Inhibitors in Cancer
Sabnis, H. S., Somasagara, R. R., & Bunting, K. D. (2017) · Genes · doi:10.3390/genes8040114 · Cited by 36 · see citing works
Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses
Li, X., Li, Y., Hao, Q., Jin, J., & Wang, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1448535 · Cited by 35 · see citing works
Overexpression of SIRT4 inhibits the proliferation of gastric cancer cells through cell cycle arrest
Hu, Y., Lin, J., Lin, Y., Chen, X., Zhu, G., & Huang, G. (2018) · Oncology Letters · doi:10.3892/ol.2018.9877 · Cited by 32 · see citing works
Bergmann, L., Lang, A., Bross, C., Altinoluk-Hambüchen, S., Fey, I., Overbeck, N., Stefanski, A., Wiek, C., Kefalas, A., Verhülsdonk, P., et al. (2020) · Cells · doi:10.3390/cells9091950 · Cited by 32 · see citing works
The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer
Onyiba, C. I., Scarlett, C. J., & Weidenhofer, J. (2022) · Cancers · doi:10.3390/cancers14205118 · Cited by 31 · see citing works
Mitochondrial sirtuins in stem cells and cancer
Jaiswal, A., Xudong, Z., Ju, Z., & Saretzki, G. C. (2021) · FEBS Journal · doi:10.1111/febs.15879 · Cited by 29 · see citing works
Targeting respiratory complex I to prevent the Warburg effect
Vatrinet, R., Iommarini, L., Kurelac, I., Luise, M. D., Gasparre, G., & Porcelli, A. M. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.01.017 · Cited by 29 · see citing works
Double hit lymphoma: from biology to therapeutic implications
Burotto, M., Berkovits, A., & Dunleavy, K. M. (2016) · Expert Review of Hematology · doi:10.1080/17474086.2016.1182858 · Cited by 28 · see citing works
Regulation of Adaptive Immune Cells by Sirtuins
Warren, J. L., & MacIver, N. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00466 · Cited by 28 · see citing works
Rinaldi, L., Donne, R. D., Borzacchiello, D., Insabato, L., & Feliciello, A. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.04.004 · Cited by 26 · see citing works
Regulation of Cancer and Cancer-Related Genes via NAD +
Sharif, T., Martell, E., Dai, C., Ghassemi-Rad, M. S., Kennedy, B. E., Lee, P. W. K., & Gujar, S. A. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7478 · Cited by 25 · see citing works
Intersections between mitochondrial sirtuin signaling and tumor cell metabolism
Herrera, K. N. G., Lee, J. J., & Haigis, M. C. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1031879 · Cited by 24 · see citing works
Self-citationMammalian Sirtuins SIRT4 and SIRT7
Li, S., & Zheng, W. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.001 · Cited by 24 · see citing works
Knockout of SIRT4 decreases chemosensitivity to 5‑FU in colorectal cancer cells
Zhu, Y., Wang, G., Li, X., Wang, T., Weng, M., & Zhang, Y. (2018) · Oncology Letters · doi:10.3892/ol.2018.8850 · Cited by 24 · see citing works
Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma
Pang, Y., Lu, T., Xu-Monette, Z. Y., & Young, K. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065493 · Cited by 25 · see citing works
Impact of Sirtuin Enzymes on the Altered Metabolic Phenotype of Malignantly Transformed Cells
Gaál, Z., & Csernoch, L. J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00045 · Cited by 22 · see citing works
Functions of mammalian SIRT4 in cellular metabolism and research progress in human cancer (Review)
Wang, C., Liu, Y., Zhu, Y., & Kong, C. (2020) · Oncology Letters · doi:10.3892/ol.2020.11872 · Cited by 22 · see citing works
Tumor-suppressive function of SIRT4 in neuroblastoma through mitochondrial damage
Wang, Y., Guo, Y., Gao, J., & Yuan, X. (2018) · Cancer Management and Research · doi:10.2147/cmar.s172509 · Cited by 20 · see citing works
Research Progress of Sirtuin4 in Cancer
Bai, Y., Yang, J., Cui, Y., Yao, Y., Wu, F., Liu, C., Fan, X., & Zhang, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.562950 · Cited by 20 · see citing works
Zeng, D., Desai, A. P., Yan, F., Gong, T., Ye, H., Ahmed, M., Nomie, K. J., Romaguera, J. E., Champlin, R. E., Li, S., et al. (2018) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000427 · Cited by 18 · see citing works
Sirtuins in B lymphocytes metabolism and function
Ghirotto, B., Terra, F. F., Câmara, N. O. S., & Basso, P. J. (2019) · World Journal of Experimental Medicine · doi:10.5493/wjem.v9.i1.1 · Cited by 17 · see citing works
Liao, P., Chang, N., Xu, B., Qiu, Y., Wang, S., Zhou, L., He, Y., Xie, X., & Li, Y. (2022) · Immunology and Cell Biology · doi:10.1111/imcb.12557 · Cited by 16 · see citing works
Tucker, S. A., Hu, S.-H., Vyas, S., Park, A., Joshi, S., Inal, A., Lam, T., Tan, E., Haigis, K. M., & Haigis, M. C. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113975 · Cited by 18 · see citing works
Self-citationThe Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis
Podyacheva, E., & Toropova, Y. G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097925 · Cited by 14 · see citing works
Metabolic Gatekeepers of Pathological B Cell Activation
Sadras, T., Chan, L. N., Xiao, G., & Müschen, M. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-061020-050135 · Cited by 14 · see citing works
A glance at the actual role of glutamine metabolism in thyroid tumorigenesis
Abooshahab, R., Hooshmand, K., Razavi, F., Dass, C. R., & Hedayati, M. (2021) · EXCLI journal · doi:10.17179/excli2021-3826 · Cited by 14 · see citing works
Nowicki, M., Wierzbowska, A., Stec‐Martyna, E., Kulczycka-Wojdala, D., Nowicki, G., & Szmigielska‐Kapłon, A. (2022) · Cancers · doi:10.3390/cancers14051213 · Cited by 12 · see citing works
Sirtuins, Healthspan, and Longevity in Mammals
Giblin, W., & Lombard, D. B. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-411596-5.00003-4 · Cited by 12 · see citing works
Amino acids in hematologic malignancies: Current status and future perspective
Wang, M., Zhao, A., Li, M., & Niu, T. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1113228 · Cited by 11 · see citing works
Xu, L., Xu, K., Xiang, L., & Yan, J. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12367 · Cited by 10 · see citing works
Sirtuin insights: bridging the gap between cellular processes and therapeutic applications
Kamal, S., Babar, S., Ali, W., Rehman, K., Hussain, A., & Akash, M. S. H. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03263-9 · Cited by 8 · see citing works
Zhou, Y., Luo, Q., Gu, L., Tian, X., Zhao, Y., Zhang, Y., & Wang, F. (2025) · Pharmaceuticals · doi:10.3390/ph18040563 · Cited by 9 · see citing works
Sirtuins Function as the Modulators in Aging-related Diseases in Common or Respectively
Wang, Q., & Guo, S. (2015) · Chinese Medical Journal · doi:10.4103/0366-6999.158375 · Cited by 8 · see citing works
Li, Y., Zhao, Y., Cao, Z., Wang, J., Liu, T., Li, Y., Wang, Y., & He, B. (2021) · RSC Advances · doi:10.1039/d0ra09424b · Cited by 7 · see citing works
Xing, W., Zhou, Y., Long, Q., Yi, N., Wang, G., Shi, R., Huang, J., Yin, X., Zhu, T., & Cao, S. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2024.1511958 · Cited by 7 · see citing works
Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer
Raghu, S., Prabhashankar, A. B., Shivanaiah, B., Tripathi, E., & Sundaresan, N. R. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-07634-3_10 · Cited by 7 · see citing works
Advances of SIRT4 in cancer metabolism and therapy
Yue, X., Shi, Y., & Luo, Q. (2023) · Pediatric Discovery · doi:10.1002/pdi3.17 · Cited by 6 · see citing works
Lessons from Using Genetically Engineered Mouse Models of MYC-Induced Lymphoma
Winkler, R., Piskor, E.-M., & Kosan, C. (2022) · Cells · doi:10.3390/cells12010037 · Cited by 6 · see citing works
The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia—A Promising Road Ahead
Strzałka, P., Krawiec, K. M., Wiśnik, A., Jarych, D., Czemerska, M., Zawlik, I., Pluta, A., & Wierzbowska, A. (2025) · Cancers · doi:10.3390/cancers17061009 · Cited by 5 · see citing works
Yang, W., van de Ven, R. A. H., & Haigis, M. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813499-3.00008-3 · Cited by 4 · see citing works
Self-citationGanai, S. A. (2020) · Springer eBooks · doi:10.1007/978-981-15-8179-3_4 · Cited by 4 · see citing works
Sirtuins and cellular metabolism in cancers
Dong, Z., & Cui, H. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822467-0.00008-5 · Cited by 3 · see citing works
Genetic Interactions of Mitochondrial Sirtuins in Brain Tumorigenesis
Haq, M. F. U., Kayani, M. A., Arshad, T., Anwar, R. A. H., Saeed, N., Shafique, R., Abbasi, S. F., Ahmed, M. W., & Mahjabeen, I. (2022) · Future Oncology · doi:10.2217/fon-2021-0264 · Cited by 3 · see citing works
Molecular, Cellular, and Physiological Characterization of Sirtuin 7 (SIRT7)
Shin, J. J., & Chen, D. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3667-0_18 · Cited by 3 · see citing works
- Authors
- Jeong, S. M., Lee, A., Lee, J., & Haigis, M. C.
- Affiliations
- Harvard University (US)
- Corresponding author
- Haigis, Marcia C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 289
- Issue
- 7
- Pages
- 4135-4144
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3924279
- OpenAlex
- W2027930781
- Cited by
- 121
- References
- 27
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 14 · 2019: 9 · 2018: 16 · 2017: 7 · 2016: 15 · 2015: 14 · 2014: 8
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG032375)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- SIRT4, c-Myc, B-cell lymphoma, Burkitt lymphoma, glutamine metabolism, tumor suppressor, mitochondrial metabolism, glutamate dehydrogenase, Eμ-myc transgenic mice, glycolysis inhibitors, glucose depletion, glutamine uptake
- MeSH terms
- Animals, Burkitt Lymphoma, Female, Glucose, Glutamate Dehydrogenase, Glutamine, Glycolysis, Humans, Male, Models, Genetic, Proto-Oncogene Proteins c-myc, Mice, Knockout, Mitochondrial Proteins, Sirtuins, Cell Line, Tumor, 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.
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