Fructose 2,6-bisphosphate is a potent endogenous stimulator of glycolysis. A high aerobic glycolytic rate often correlates with increased cell proliferation. To investigate this relationship, we have produced clonal cell lines of Rat-1 fibroblasts that stably express transgenes coding for 6-phosphofructo-2-kinase, which catalyzes the synthesis of fructose 2,6-bisphosphate, or for fructose 2,6-bisphosphatase, which catalyzes its degradation. While serum deprivation in culture reduced the growth rate of control cells, it caused apoptosis in cells overproducing fructose 2,6-bisphosphate. Apoptosis was inhibited by 5-amino-4-imidazolecarboxamide riboside, suggesting that 5'-AMP-activated protein kinase interferes with this phenomenon.
Durante, P., Gueuning, M.-A., Darville, M. I., Hue, L., & Rousseau, G. (1999). Apoptosis induced by growth factor withdrawal in fibroblasts overproducing fructose 2,6-bisphosphate. FEBS Letters, 448(2-3), 239-243. https://doi.org/10.1016/S0014-5793(99)00387-7 (Original work published 1999)