title: Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progression.
abstract: 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.
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
authors.forename: J X
authors.initials: JX
authors.lastname: Perez
authors.forename: T
authors.initials: T
authors.lastname: Roig
authors.forename: A
authors.initials: A
authors.lastname: Manzano
authors.forename: M
authors.initials: M
authors.lastname: Dalmau
authors.forename: J
authors.initials: J
authors.lastname: Boada
authors.forename: F
authors.initials: F
authors.lastname: Ventura
authors.forename: J L
authors.initials: JL
authors.lastname: Rosa
authors.forename: J
authors.initials: J
authors.lastname: Bermudez
authors.forename: R
authors.initials: R
authors.lastname: Bartrons
mesh_terms: 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
chemical_list: D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005631:Fructokinases; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases