Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progression |
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Authors: | Perez J X Roig T Manzano A Dalmau M Boada J Ventura F Rosa J L Bermudez J Bartrons R |
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Institution: | Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain. |
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Abstract: | The ability to overexpress6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase(PFK-2)/(FBPase-2) or a truncated form of the enzyme with only thebisphosphatase domain allowed us to analyze the relative role of thekinase and the bisphosphatase activities in regulating fructose2,6-bisphosphate (Fru-2,6-P2) concentration and toelucidate their differential metabolic impact in epithelial Mv1Lucells. The effect of overexpressing PFK-2/FBPase-2 resulted in a smallincrease in the kinase activity and in the activity ratio of thebifunctional enzyme, increasing Fru-2,6-P2 levels, butthese changes had no major effects on cell metabolism. In contrast,expression of the bisphosphatase domain increased the bisphosphataseactivity, producing a significant decrease in Fru-2,6-P2 concentration. The fall in the bisphosphorylated metabolite correlated with a decrease in lactate production and ATP concentration, as well asa delay in cell cycle. These results provide support for Fru-2,6-P2 as a regulator of glycolytic flux and point outthe role of glycolysis in cell cycle progression. |
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