Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia

Abstract : Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux.
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Scientific Reports, Nature Publishing Group, 2016, 6, pp.35561. 〈10.1038/srep35561〉
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http://hal.univ-grenoble-alpes.fr/hal-01398304
Contributeur : Frank Thomas <>
Soumis le : jeudi 17 novembre 2016 - 09:45:04
Dernière modification le : lundi 19 février 2018 - 14:34:03

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Delphine Ohayon, Alessia De Chiara, Nicolas Chapuis, Céline Candalh, Julie Mocek, et al.. Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia. Scientific Reports, Nature Publishing Group, 2016, 6, pp.35561. 〈10.1038/srep35561〉. 〈hal-01398304〉

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