E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation
Open accessAbstract
Cell proliferation is known to be accompanied by activation of glycolysis. We have recently discovered that the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1, which also degrades cell-cycle proteins. We now show in two different cell types (neoplastic and nonneoplastic) that both proliferation and aerobic glycolysis are prevented by overexpression of Cdh1 and enhanced by its silencing. Furthermore, we have coexpressed Cdh1 with PFKFB3—either wild-type or a mutant form resistant to ubiquitylation by APC/C-Cdh1—or with the glycolytic enzyme 6-phosphofructo-1-kinase and demonstrated that whereas glycolysis is essential for cell proliferation, its initiation in the presence of active Cdh1 does not result in proliferation. Our experiments indicate that the proliferative response, regardless of whether it occurs in normal or neoplastic cells, is dependent on a decrease in the activity of APC/C-Cdh1, which activates both proliferation and glycolysis. These observations have implications for cell proliferation, neoplastic transformation, and the prevention and treatment of cancer.
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Protein levels of Pfkfb3 are low in neurons because of its constant proteasomal degradation.
“Protein levels of Pfkfb3 are low in neurons because of its constant proteasomal degradation (Herrero-Mendez et al., 2009;Almeida et al., 2010)”
From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Almeida et al., 2010
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Cites
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078 · see citing works
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
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295 · see citing works
Cyclin is degraded by the ubiquitin pathway
Glotzer, M., Murray, A. W., & Kirschner, M. W. (1991) · Nature · doi:10.1038/349132a0 · Cited by 2,381 · see citing works
A Restriction Point for Control of Normal Animal Cell Proliferation
Pardee, A. B. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.4.1286 · Cited by 1,416 · see citing works
The anaphase promoting complex/cyclosome: a machine designed to destroy
Peters, J.-M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1988 · Cited by 1,315 · see citing works
Herrero-Mendez, A., Almeida, A., Fernández, E., Maestre, C., Moncada, S., & Bolaños, J. P. (2009) · Nature Cell Biology · doi:10.1038/ncb1881 · Cited by 844 · see citing works
Self-citationThe KEN box: an APC recognition signal distinct from the D box targeted by Cdh1Preprint
Pfleger, C. M., & Kirschner, M. W. (2000) · Genes & Development · doi:10.1101/gad.14.6.655 · Cited by 733 · see citing works
Almeida, Á., Moncada, S., & Bolaños, J. P. (2003) · Nature Cell Biology · doi:10.1038/ncb1080 · Cited by 481 · see citing works
Self-citationRegulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer
Yalçın, A., Telang, S., Clem, B. F., & Chesney, J. A. (2009) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2009.01.003 · Cited by 407 · see citing works
Zetterberg, A., & Larsson, O. S. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.16.5365 · Cited by 372 · see citing works
Genomic stability and tumour suppression by the APC/C cofactor Cdh1
García-Higuera, I., Manchado, E., Dubus, P. R., Cañamero, M., Méndez, J., Moreno, S., & Malumbres, M. (2008) · Nature Cell Biology · doi:10.1038/ncb1742 · Cited by 357 · see citing works
Aerobic glycolysis during lymphocyte proliferation
Wang, T., Marquardt, C. A., & Foker, J. E. (1976) · Nature · doi:10.1038/261702a0 · Cited by 333 · see citing works
Yalçın, A., Clem, B. F., Simmons, A. J., Lane, A. N., Nelson, K. K., Clem, A. L., Brock, E., Siow, D. L., Wattenberg, B. W., Telang, S., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016816 · Cited by 242 · see citing works
Aerobic glycolysis and lymphocyte transformation
Hume, D. A., Radik, J., Ferber, E., & Weidemann, M. J. (1978) · Biochemical Journal · doi:10.1042/bj1740703 · Cited by 172 · see citing works
Cdh1/Hct1-APC Is Essential for the Survival of Postmitotic Neurons
Almeida, Á., Bolaños, J. P., & Moreno, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1143-05.2005 · Cited by 155 · see citing works
Self-citationThe function of APC/CCdh1 in cell cycle and beyond
Li, M., & Zhang, P. (2009) · Cell Division · doi:10.1186/1747-1028-4-2 · Cited by 112 · see citing works
Alterations of anaphase-promoting complex genes in human colon cancer cells
Wang, Q., Moyret‐Lalle, C., Couzon, F., Surbiguet-Clippe, C., Saurin, J., Lorca, T., Navarro, C., & Puisieux, A. (2003) · Oncogene · doi:10.1038/sj.onc.1206224 · Cited by 107 · see citing works
Yamano, H., Tsurumi, C., Gannon, J., & Hunt, T. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5670 · Cited by 105 · see citing works
Cell cycle‐dependent nuclear export of Cdh1p may contribute to the inactivation of APC/CCdh1
Jaquenoud, M., van Drogen, F., & Peter, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf634 · Cited by 105 · see citing works
Cuende, J., Moreno, S., Bolaños, J. P., & Almeida, Á. (2008) · Oncogene · doi:10.1038/sj.onc.1210987 · Cited by 70 · see citing works
Self-citationWang, C.-X., Fisk, B. C., Wadehra, M., Su, H. C., & Braun, J. G. (2000) · Blood · doi:10.1182/blood.v96.1.259 · Cited by 51 · see citing works
Park, K. H., Choi, S., Eom, M., & KANG, Y. Y. (2005) · Breast Cancer Research · doi:10.1186/bcr978 · Cited by 45 · see citing works
The Importance of Changes in Membrane Transport in Lymphocyte Activation by Phytohaemagglutinin
Kay, J. E. (1976) · Biochemical Society Transactions · doi:10.1042/bst0041120 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
“Protein levels of Pfkfb3 are low in neurons because of its constant proteasomal degradation (Herrero-Mendez et al., 2009; Almeida et al., 2010),and,consistentwith these observations, we found that Pfkfb3 mRNA is enriched by an order of magnitude in astrocytes compared with neurons.”
BackgroundSIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity
Kim, H., Vassilopoulos, A., Wang, R.-H., Lahusen, T. J., Xiao, Z., Xu, X., Li, C., Veenstra, T. D., Li, B., Yu, H., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.004 · Cited by 536 · see citing works
Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 502 · see citing works
Mitochondrial Regulation of Cell Cycle and Proliferation
Arciuch, V. G. A., Elguero, M. E., Poderoso, J. J., & Carreras, M. C. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4085 · Cited by 428 · see citing works
Role of Endothelial Cell Metabolism in Vessel Sprouting
Bock, K. D., Γεωργιάδου, Μ., & Carmeliet, P. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.001 · Cited by 428 · see citing works
Targeting cell cycle regulation in cancer therapy
Díaz‐Moralli, S., Tarrado‐Castellarnau, M., Miranda, A., & Cascante, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.011 · Cited by 361 · see citing works
Yang, Z., Fujii, H., Mohan, S. V., Goronzy, J. J., & Weyand, C. M. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130252 · Cited by 334 · see citing works
Control of Glycolysis through Regulation of PFK1: Old Friends and Recent AdditionsPreprint
Mor, I., Cheung, E. C., & Vousden, K. H. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010868 · Cited by 316 · see citing works
Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis
Andrabi, S. A., Umanah, G. K. E., Chang, C., Stevens, D. A., Karuppagounder, S. S., Gagné, J.-P., Poirier, G. G., Dawson, V. L., & Dawson, T. M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405158111 · Cited by 307 · see citing works
Fueling the Cell Division Cycle
Salazar‐Roa, M., & Malumbres, M. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.08.009 · Cited by 270 · see citing works
Ros, S., & Schulze, A. (2013) · Cancer & Metabolism · doi:10.1186/2049-3002-1-8 · Cited by 269 · see citing works
Sánchez-Cenizo, L., Formentini, L., Aldea, M., Ortega, A. D., García-Huerta, P., Sánchez‐Aragó, M., & Cuezva, J. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.146480 · Cited by 220 · see citing works
The engine driving the ship: metabolic steering of cell proliferation and death
Buchakjian, M. R., & Kornbluth, S. A. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2972 · Cited by 215 · see citing works
How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions?
Lincet, H., & Icard, P. (2014) · Oncogene · doi:10.1038/onc.2014.320 · Cited by 207 · see citing works
Revisiting the role of metabolism during development
Miyazawa, H., & Aulehla, A. (2018) · Development · doi:10.1242/dev.131110 · Cited by 188 · see citing works
Yalçın, A., Clem, B. F., Imbert-Fernandez, Y., Özcan, S. C., Peker, S., O’Neal, J., Klarer, A. C., Clem, A. L., Telang, S., & Chesney, J. A. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.292 · Cited by 199 · see citing works
Li, F., Liu, J., Bao, R., Yan, G., Feng, X., Xu, Y., Sun, Y., Yan, W., Ling, Z., Xiong, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02950-5 · Cited by 197 · see citing works
McBrayer, S. K., Cheng, J. C., Singhal, S., Krett, N. L., Rosen, S. T., & Shanmugam, M. (2012) · Blood · doi:10.1182/blood-2011-09-377846 · Cited by 193 · see citing works
Metabolic differentiation in the embryonic retina
Agathocleous, M., Love, N. K., Randlett, O., Harris, J. J., Liu, J., Murray, A. J., & Harris, W. A. (2012) · Nature Cell Biology · doi:10.1038/ncb2531 · Cited by 182 · see citing works
Lane, N. J. (2011) · BioEssays · doi:10.1002/bies.201100051 · Cited by 177 · see citing works
Hagenbuchner, J., Kuznetsov, A. V., Obexer, P., & Ausserlechner, M. J. (2012) · Oncogene · doi:10.1038/onc.2012.500 · Cited by 175 · see citing works
Colombo, S. L., Palacios‐Callender, M., Frakich, N., Carcamo, S., Kovacs, I., Tudzarova, S., & Moncada, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117500108 · Cited by 171 · see citing works
Self-citationAMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression
Zhao, H., Li, T., Wang, K., Zhao, F. L., Chen, J., Xu, G., Zhao, J., Li, T., Chen, L., Li, L., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0296-3 · Cited by 149 · see citing works
Ma, X., Wang, L., Huang, D., Li, Y., Yang, D., Li, T., Li, F., Sun, L., Wei, H., He, K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01647-5 · Cited by 140 · see citing works
Wei, J., Huang, K., Chen, Z., Hu, M., Bai, Y., Lin, S., & Du, H. (2020) · Cancers · doi:10.3390/cancers12071788 · Cited by 141 · see citing works
Tudzarova, S., Colombo, S. L., Stoeber, K., Carcamo, S., Williams, G. H., & Moncada, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102247108 · Cited by 136 · see citing works
Self-citationFructose 2,6-Bisphosphate in Cancer Cell Metabolism
Bartrons, R., Simon‐Molas, H., Rodríguez‐García, A., Castaño, E., Navarro‐Sabaté, À., Manzano, À., & Martinez‐Outschoorn, U. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00331 · Cited by 134 · see citing works
Colombo, S. L., Palacios‐Callender, M., Frakich, N., de León, J., Schmitt, C. A., Boorn, L., Davis, N., & Moncada, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012362107 · Cited by 126 · see citing works
Self-citationInsights into APC/C: from cellular function to diseases and therapeutics
Zhou, Z., He, M., Shah, A. A., & Wan, Y. (2016) · Cell Division · doi:10.1186/s13008-016-0021-6 · Cited by 125 · see citing works
The Emerging Facets of Non-Cancerous Warburg Effect
Abdel‐Haleem, A. M., Lewis, N. E., Jamshidi, N., Mineta, K., Gao, X., & Gojobori, T. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00279 · Cited by 121 · see citing works
APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis
Schrock, M. S., Stromberg, B. R., Scarberry, L., & Summers, M. K. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.03.001 · Cited by 119 · 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
Skp2 dictates cell cycle-dependent metabolic oscillation between glycolysis and TCA cycle
Liu, J., Peng, Y., Shi, L., Wan, L., Inuzuka, H., Long, J., Guo, J., Zhang, J., Yuan, M., Zhang, S., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0372-z · Cited by 113 · see citing works
Gerlinger, M., Santos, C. R., Spencer‐Dene, B., Martinez, P., Endesfelder, D., Burrell, R. A., Vetter, M. H. F., Jiang, M., Saunders, R. E., Kelly, G. P., et al. (2012) · The Journal of Pathology · doi:10.1002/path.4006 · Cited by 107 · see citing works
Furtado, C. M., Marcondes, M. C., Sola‐Penna, M., de Souza, M. L. S., & Zancan, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030462 · Cited by 106 · see citing works
Metabolic control of the cell cycle
Kalucka, J. M., Missiaen, R., Γεωργιάδου, Μ., Schoors, S., Lange, C. M., Bock, K. D., Dewerchin, M. A., & Carmeliet, P. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1090068 · Cited by 105 · see citing works
O’Neal, J., Clem, A. L., Reynolds, L., Dougherty, S. M., Imbert-Fernandez, Y., Telang, S., Chesney, J. A., & Clem, B. F. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-3968-8 · Cited by 105 · 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
Miquel, E., Cassina, A., Palma, L. M., Bolatto, C., Trías, E., Gandelman, M., Radí, R., Barbeito, L., & Cassina, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034776 · Cited by 102 · see citing works
Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability
Horn, S. R. G.-V., Thomenius, M. J., Johnson, E. S., Freel, C. D., Wu, J. Q., Coloff, J. L., Yang, C., Tang, W., An, J., Ilkayeva, O., et al. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-07-0567 · Cited by 101 · see citing works
Two-way communication between the metabolic and cell cycle machineries: the molecular basis
Kaplon, J., van Dam, L., & Peeper, D. S. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1044172 · Cited by 97 · see citing works
De novo fatty acid synthesis at the mitotic exit is required to complete cellular division
Scaglia, N., Tyekucheva, S., Zadra, G., Photopoulos, C., & Loda, M. F. (2014) · Cell Cycle · doi:10.4161/cc.27767 · Cited by 96 · see citing works
Du, J., Wang, L., Wang, Q., & Yu, L. (2015) · Oncology Reports · doi:10.3892/or.2015.3797 · Cited by 96 · see citing works
Mechanisms of regulation of PFKFB expression in pancreatic and gastric cancer cells
Minchenko, О. H. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i38.13705 · Cited by 94 · see citing works
Metabolic pathway compartmentalization: an underappreciated opportunity?
Zecchin, A., Stapor, P. C., Goveia, J., & Carmeliet, P. (2014) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.11.022 · Cited by 92 · see citing works
The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs
Puckett, D. L., Alquraishi, M. I., Chowanadisai, W., & Bettaieb, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031171 · Cited by 93 · see citing works
Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism
Stapor, P. C., Wang, X., Goveia, J., Moens, S., & Carmeliet, P. (2014) · Journal of Cell Science · doi:10.1242/jcs.153908 · Cited by 90 · see citing works
Structural insights into anaphase-promoting complex function and mechanism
Barford, D. (2011) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0069 · Cited by 90 · see citing works
Birts, C. N., Nijjar, S. K., Mardle, C. A., Hoakwie, F., Duriez, P. J., Blaydes, J. P., & Tavassoli, A. (2013) · Chemical Science · doi:10.1039/c3sc50481f · Cited by 85 · see citing works
Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle
Ahn, E., Kumar, P., Mukha, D., Tzur, A., & Shlomi, T. (2017) · Molecular Systems Biology · doi:10.15252/msb.20177763 · Cited by 85 · see citing works
Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
Sánchez‐Aragó, M., Formentini, L., Martínez‐Reyes, I., García‐Bermúdez, J., Santacatterina, F., Sánchez-Cenizo, L., Willers, I. M., Aldea, M., Nájera, L., Juarranz, Á., et al. (2013) · Oncogenesis · doi:10.1038/oncsis.2013.9 · Cited by 83 · see citing works
Fulfilling the metabolic requirements for cell proliferation
Moncada, S., Higgs, E. A., & Colombo, S. L. (2012) · Biochemical Journal · doi:10.1042/bj20120427 · Cited by 83 · see citing works
Self-citationThe paradox of metabolism in quiescent stem cells
Coller, H. A. (2019) · FEBS Letters · doi:10.1002/1873-3468.13608 · Cited by 82 · see citing works
Targeting PFKFB3 alleviates cerebral ischemia-reperfusion injury in mice
Burmistrova, O., Olias-Arjona, A., Lapresa, R., Jiménez-Blasco, D., Eremeeva, T. P., Shishov, D., Romanov, S., Александровна, З. К., Almeida, Á., Fedichev, P. O., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-48196-z · Cited by 80 · see citing works
Self-citationNon-mitotic functions of the Anaphase-Promoting Complex
Eguren, M., Manchado, E., & Malumbres, M. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.03.010 · Cited by 77 · see citing works
Vella, S., Conti, M., Tasso, R., Cancedda, R., & Pagano, A. (2011) · International Journal of Cancer · doi:10.1002/ijc.26173 · Cited by 73 · see citing works
Hipkiss, A. R., Cartwright, S. P., Bromley, C., Gross, S. R., & Bill, R. M. (2013) · Chemistry Central Journal · doi:10.1186/1752-153x-7-38 · Cited by 71 · see citing works
Manganese Superoxide Dismutase Regulates a Metabolic Switch during the Mammalian Cell Cycle
Sarsour, E. H., Kalen, A. L., Xiao, Z., Veenstra, T. D., Chaudhuri, L., Venkataraman, S., Reigan, P., Buettner, G. R., & Goswami, P. C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-1063 · Cited by 69 · see citing works
Melatonin and the von Hippel–Lindau/HIF-1 oxygen sensing mechanism: A review
Vriend, J. P., & Reiter, R. J. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.02.004 · Cited by 64 · see citing works
Willers, I. M., & Cuezva, J. M. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.016 · Cited by 62 · see citing works
Geroncogenesis: Metabolic Changes during Aging as a Driver of Tumorigenesis
Wu, L. E., Gomes, A. P., & Sinclair, D. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2013.12.005 · Cited by 61 · see citing works
Reid, M. A., Lowman, X. H., Pan, M., Tran, T. Q., Warmoes, M. O., Gabra, M. B. I., Yang, Y., Locasale, J. W., & Kong, M. (2016) · Genes & Development · doi:10.1101/gad.287235.116 · Cited by 62 · see citing works
DeSalvo, J., Kuznetsoff, J. N., Du, J., Leclerc, G. M., Leclerc, G. J., Lampidis, T. J., & Barredo, J. C. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0125 · Cited by 61 · see citing works
The Glycolytic Enzyme PFKFB3 Is Involved in Estrogen-Mediated Angiogenesis via GPER1
Trenti, A., Tedesco, S., Boscaro, C., Ferri, N., Cignarella, A., Trevisi, L., & Bolego, C. (2017) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.238212 · Cited by 61 · see citing works
Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth
Zhao, J., Shi, S., Qu, H.-Y., Keckesova, Z., Cao, Z.-J., Yang, L., Yu, X., Feng, L., Shi, Z., Krakowiak, J., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-021-00524-2 · Cited by 58 · see citing works
The Role of the Anaphase-Promoting Complex/Cyclosome in Plant Growth
Eloy, N. B., Lima, M. D. F., Ferreira, P. C. G., & Inzé, D. (2015) · Critical Reviews in Plant Sciences · doi:10.1080/07352689.2015.1078613 · Cited by 55 · see citing works
Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism
Koo, S.-Y., Park, E., Noh, H.-J., Jo, S.-M., Ko, B.-K., Shin, H.-J., & Lee, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098441 · Cited by 56 · see citing works
The mitochondrial bioenergetic capacity of carcinomas
Formentini, L., Martínez‐Reyes, I., & Cuezva, J. M. (2010) · IUBMB Life · doi:10.1002/iub.352 · Cited by 54 · see citing works
de Tudela, M. V.-P., Delgado‐Esteban, M., Maestre, C., Bobo-Jiménez, V., Jiménez-Blasco, D., Vecino, R., Bolaños, J. P., & Almeida, Á. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4712-14.2015 · Cited by 55 · see citing works
Self-citationIncomplete and transitory decrease of glycolysis
Schoors, S., Cantelmo, A. R., Γεωργιάδου, Μ., Stapor, P. C., Wang, X., Quaegebeur, A., Cauwenberghs, S., Wong, B. W., Bifari, F., Decimo, I., et al. (2013) · Cell Cycle · doi:10.4161/cc.27519 · Cited by 53 · see citing works
Novellasdemunt, L., Obach, M., Millán-Ariño, L., Manzano, À., Ventura, F., Rosa, J. L., Jordan, A., Navarro‐Sabaté, À., & Bartrons, R. (2011) · Biochemical Journal · doi:10.1042/bj20111418 · Cited by 52 · see citing works
Tarabichi, M., Antoniou, A., Saiselet, M., Pita, J. M. G., Andry, G., Dumont, J. E., Detours, V., & Maenhaut, C. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9431-y · Cited by 50 · see citing works
Coordination of cell growth and division by the ubiquitin–proteasome system
Benanti, J. A. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.04.005 · Cited by 51 · see citing works
Park, S., Lee, M. J., Lee, S. J., Yun, S. J., Jang, J.-Y., Kang, H., Kim, K. H., & Choi, I. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s94907 · Cited by 51 · see citing works
Cordero-Espinoza, L., & Hagen, T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.510289 · Cited by 50 · see citing works
Kwiatkowska, E., Wojtala, M., Gajewska, A., Soszyński, M., Bartosz, G., & Sadowska‐Bartosz, I. (2015) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-015-9637-5 · Cited by 50 · see citing works
Improving Homology-Directed Repair in Genome Editing Experiments by Influencing the Cell Cycle
Smirnikhina, S., Zaynitdinova, M. I., Sergeeva, V. A., & Лавров, А. В. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23115992 · Cited by 48 · see citing works
Swerdlow, R. H. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12394 · Cited by 50 · see citing works
PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis
Pegoraro, C., Figueiredo, A. L., Maczkowiak, F., Pouponnot, C., Eychène, A., & Monsoro-Burq, A. H. (2015) · Nature Communications · doi:10.1038/ncomms6953 · Cited by 48 · see citing works
Fueling the Cycle: CDKs in Carbon and Energy Metabolism
Solaki, M., & Ewald, J. C. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00093 · Cited by 47 · see citing works
Cieślar‐Pobuda, A., Jain, M. V., Kratz, G., Rzeszowska‐Wolny, J., Ghavami, S., & Wiecheć, E. (2015) · Oncotarget · doi:10.18632/oncotarget.4995 · Cited by 46 · see citing works
The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis
Woo, M. S., Brand, J., Bal, L. C., Moritz, M., Walkenhorst, M., Vieira, V., Ipenberg, I., Rothammer, N., Wang, M., Dogan, B., et al. (2025) · Cell · doi:10.1016/j.cell.2025.05.029 · Cited by 46 · see citing works
Lv, Y., Zhang, B., Zhai, C., Qiu, J. F., Zhang, Y., Yao, W., & Zhang, C. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.10.006 · Cited by 44 · see citing works
Patterns of Amino Acid Metabolism by Proliferating Human Mesenchymal Stem Cells
Higuera, G. A., Schop, D., Spitters, T. W. G. M., van Dijkhuizen-Radersma, R., Bracke, M., de Bruijn, J. D., Martens, D. E., Karperien, M., van Boxtel, A. J. B., & van Blitterswijk, C. (2011) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0223 · Cited by 44 · 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
Uncoupling the Warburg effect from cancer
Najafov, A., & Alessi, D. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014047107 · Cited by 39 · see citing works
APC/C Ubiquitin Ligase: Coupling Cellular Differentiation to G1/G0 Phase in Multicellular Systems
Kimata, Y. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.03.001 · Cited by 38 · see citing works
Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy
Smolders, L., & Teodoro, J. G. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.558008 · Cited by 37 · see citing works
Hernández‐Reséndiz, I., Gallardo‐Pérez, J. C., López-Macay, Á., Robledo‐Cadena, D. X., Garcı́a-Villa, E., Gariglio, P., Saavedra, E., Moreno‐Sánchez, R., & Rodríguez‐Enríquez, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27354 · Cited by 35 · see citing works
The Many Facets of Tumor Heterogeneity: Is Metabolism Lagging Behind?
Loponte, S., Lovisa, S., Deem, A. K., Carugo, A., & Viale, A. (2019) · Cancers · doi:10.3390/cancers11101574 · Cited by 34 · see citing works
New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in Alzheimer’s Disease
Fuchsberger, T., Lloret, A., & Viña, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18051057 · Cited by 33 · see citing works
Neuroprotective coordination of cell mitophagy by the ATPase Inhibitory Factor 1
Matić, I., Cocco, S., Ferraina, C., Martín-Jiménez, R., Florenzano, F., Crosby, J., Lupi, R., Amadoro, G., Russell, C., Pignataro, G., et al. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.10.010 · Cited by 29 · see citing works
Hidden targets of ubiquitin proteasome system: To prevent diabetic nephropathy
Goru, S. K., Kadakol, A., & Gaikwad, A. B. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.03.024 · Cited by 29 · see citing works
Li, Q., Chen, Y., Liu, H., Tian, Y., Yin, G., & Xie, Q. (2023) · Inflammation Research · doi:10.1007/s00011-023-01807-y · Cited by 28 · see citing works
Zhu, S., Gu, H., Peng, C. Y., Xia, F., Cao, H., & Cui, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.849625 · Cited by 29 · see citing works
Klepinin, A., Chekulayev, V. A., Timohhina, N., Shevchuk, I. N., Tepp, K., Kaldma, A., Koit, A., Saks, V. A., & Käämbre, T. (2013) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-013-9529-5 · Cited by 28 · see citing works
Shen, Y., Sherman, J. W., Chen, X., & Wang, R. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001379 · Cited by 27 · see citing works
Non‐genomic mechanisms in the estrogen regulation of glycolytic protein levels in endothelial cells
Boscaro, C., Carotti, M., Albiero, M., Trenti, A., Fadini, G. P., Trevisi, L., Sandonà, D., Cignarella, A., & Bolego, C. (2020) · The FASEB Journal · doi:10.1096/fj.202001130r · Cited by 27 · see citing works
AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease
Pardo, B., Herrada-Soler, E., Satrústegui, J., Contreras, L., & del Arco, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23010528 · Cited by 27 · see citing works
Garedew, A., Andreassi, C., & Moncada, S. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.003 · Cited by 24 · see citing works
Self-citationRetracted
- Authors
- Almeida, A., Bolaños, J. P., & Moncada, S.
- Affiliations
- Hospital Universitario de Salamanca, Instituto de Estudios de Ciencias de la Salud de Castilla y Leon, 37007 Salamanca, Spain;
- Universidad de Salamanca (ES)
- University College London (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12-22
- Volume
- 107
- Issue
- 2
- Pages
- 738-741
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2818939
- OpenAlex
- W2167058369
- Cited by
- 166
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 9 · 2015: 16 · 2014: 12 · 2013: 21 · 2012: 20
- FWCI
- 4.59
- 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)
- Research Explorer (The University of Manchester) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Ministerio de Ciencia e Innovación (CSD2007-00020)
- Junta de Castilla y León
- Instituto de Salud Carlos III (2008-2011, CSD2007-00020)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- APC/C-Cdh1, E3 ubiquitin ligase, CDH1, Warburg effect, aerobic glycolysis, PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, 6-phosphofructokinase, cell proliferation, ubiquitination, oncogenic transformation, cancer
- MeSH terms
- Aerobiosis, Cell Cycle, Cell Division, Gene Expression Regulation, Glycolysis, Humans, Kidney, Neuroblastoma, Phosphofructokinase-1, Tretinoin, Antigens, CD, Cadherins, Gene Expression Regulation, Neoplastic, Cell Cycle Proteins, Phosphofructokinase-2, Ubiquitin-Protein Ligases, Cell Line, Tumor
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