Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progression.
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.
Perez
J X
JX
Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
Roig
T
T
Manzano
A
A
Dalmau
M
M
Boada
J
J
Ventura
F
F
Rosa
J L
JL
Bermudez
J
J
Bartrons
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005631:Fructokinases / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D019344:Lactic Acid / Q000378:metabolism; D008907:Mink; D009994:Osmolar Concentration; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D013997:Time Factors
D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005631:Fructokinases; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases