E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation

Angeles Almeida, Juan P. Bolaños, Salvador Moncada

    Research output: Contribution to journalArticlepeer-review


    Cell proliferation is known to be accompanied by activation of glycolysis.Wehaverecently discoveredthat theglycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, iso-form 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 thatwhereas 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.
    Original languageEnglish
    Pages (from-to)738-741
    Number of pages3
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number2
    Publication statusPublished - 2010


    • Aerobic glycolysis
    • Cancer
    • Cell cycle
    • PFKFB3


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