The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
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.
Overview
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
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078
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
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
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
Cyclin is degraded by the ubiquitin pathway
Glotzer, M., Murray, A. W., & Kirschner, M. W. (1991) · Nature · doi:10.1038/349132a0 · Cited by 2,359
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
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
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
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
Almeida, Á., Moncada, S., & Bolaños, J. P. (2003) · Nature Cell Biology · doi:10.1038/ncb1080 · Cited by 481
Self-citation
Research works printed but not linked: 2
- DO Morgan The Cell Cycle, ed E Lawrence (New Science, London, 2007).
- 10.1182/blood.V96.1.259.013k36_259_263 · DOI
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
“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
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 521
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 449
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 437
Metadata
- 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
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
