Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progression

1  Unitat de Bioquímica, 2  Unitat de Biofísica, 3  Laboratori de Citometria, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain The ability to overexpress 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2)/(FBPase-2) or a truncated fo...

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Published in:American Journal of Physiology: Cell Physiology 2000-11, Vol.279 (5), p.C1359-C1365
Main Authors: Perez, J. Xavier, Roig, Teresa, Manzano, Anna, Dalmau, Mireia, Boada, Jordi, Ventura, Francesc, Rosa, Jose L, Bermudez, Jordi, Bartrons, Ramon
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Cell Cycle - physiology
Cell Line
Epithelial Cells - metabolism
Fructokinases - metabolism
Glycolysis - physiology
Lactic Acid - metabolism
Mink
Osmolar Concentration
Phosphofructokinase-2
Phosphoric Monoester Hydrolases - metabolism
Time Factors
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Summary:1  Unitat de Bioquímica, 2  Unitat de Biofísica, 3  Laboratori de Citometria, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain The ability to overexpress 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2)/(FBPase-2) or a truncated form of the enzyme with only the bisphosphatase domain allowed us to analyze the relative role of the kinase and the bisphosphatase activities in regulating fructose 2,6-bisphosphate (Fru-2,6-P 2 ) concentration and to elucidate their differential metabolic impact in epithelial Mv1Lu cells. The effect of overexpressing PFK-2/FBPase-2 resulted in a small increase in the kinase activity and in the activity ratio of the bifunctional enzyme, increasing Fru-2,6-P 2 levels, but these changes had no major effects on cell metabolism. In contrast, expression of the bisphosphatase domain increased the bisphosphatase activity, producing a significant decrease in Fru-2,6-P 2 concentration. The fall in the bisphosphorylated metabolite correlated with a decrease in lactate production and ATP concentration, as well as a delay in cell cycle. These results provide support for Fru-2,6-P 2 as a regulator of glycolytic flux and point out the role of glycolysis in cell cycle progression. metabolism; 6-phosphofructo-2-kinase
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.2000.279.5.C1359