Increase in Fru-2,6-P(2) levels results in altered cell division in Schizosaccharomyces pombe.
Mitogenic response to growth factors is concomitant with the modulation they exert on the levels of Fructose 2,6-bisphosphate (Fru-2,6-P2), an essential activator of the glycolytic flux. In mammalian cells, decreased Fru-2,6-P2 concentration causes cell cycle delay, whereas high levels of Fru-2,6-P2 sensitize cells to apoptosis. In order to analyze the cell cycle consequences due to changes in Fru-2,6-P2 levels, the bisphosphatase-dead mutant (H258A) of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase enzyme was over-expressed in Schizosaccharomyces pombe cells and the variation in cell phenotype was studied. The results obtained demonstrate that the increase in Fru-2,6-P2 levels results in a defective division of S. pombe, as revealed by an altered multisepted phenotype. The H258A-expressing cells showed impairment of cytokinesis, but normal nuclear division. In order to identify cellular mediators responsible for this effect, we transformed different S. pombe strains and observed that the cytokinetic defect was absent in cells defective for Wee1 kinase function. Therefore, in S. pombe, Wee1 integrates the metabolic signal emerging from changes in Fru-2,6-P2 content, thus coupling metabolism with cell proliferation. As the key regulators of the cell cycle checkpoints are conserved throughout evolution, these results may help to understand the experimental evidences obtained by manipulation of Fru-2,6-P2 levels in mammalian cells.
Fernández de Mattos
Silvia
S
Cancer Cell Biology and Translational Oncology Group, Institut Universitari d'Investigació en Ciències de la Salut, Departament de Biologia Fonamental, Universitat de les Illes Balears, Illes Balears, Spain. silvia.fernandez@uib.es
Alemany
Vicenç
V
Aligué
Rosa
R
Tauler
Albert
A
D002455:Cell Division; D005635:Fructosediphosphates / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D009154:Mutation / Q000235:genetics; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D005635:Fructosediphosphates; D029702:Schizosaccharomyces pombe Proteins; D015534:Trans-Activators; C087051:rep1 protein, S pombe; C027652:fructose 2,6-diphosphate; D025481:Phosphofructokinase-2