Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes

Sergio L. Colombo, Miriam Palacios-Callender, Nanci Frakich, Joel De Leon, Christoph A. Schmitt, Leanne Boorn, Nicola Davis, Salvador Moncada

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Cell proliferation is accompanied by an increase in the utilization of glucose and glutamine. The proliferative response is dependent on a decrease in the activity of the ubiquitin ligase anaphasepromoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably the KEN box. This occurs not only in cell cycle proteins but also in the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase isoform 3 (PFKFB3), as we have recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of human T lymphocytes. Moreover, we have found that glutaminase 1 is a substrate for this ubiquitin ligase and appears at the same time as PFKFB3 in proliferating T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision not only of glucose but also of glutamine and, as such, accounts for the critical step that links the cell cycle with the metabolic substrates essential for its progression.
    Original languageEnglish
    Pages (from-to)18868-18873
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume107
    Issue number44
    DOIs
    Publication statusPublished - 2 Nov 2010

    Keywords

    • 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3
    • Cell cycle
    • Glutaminase
    • Proliferation

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