An E2F-dependent late-serum-response promoter in a gene that controls glycolysis

The F-type mRNA of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is found in proliferating, but not in quiescent, cells. This bifunctional enzyme catalyses the synthesis and degradation of fructose-2,6-bisphosphate, a potent stimulator of glycolysis. F-type mRNA concentration decreased upon differentiation of rat rhabdomyosarcoma cells; it increased in Rat-1 fibroblasts stimulated to proliferate by serum, by epidermal growth factor, or by the v-src oncogene product. This increase resulted, at least in part, from a stimulation of F promoter activity. The stimulation occurred at the G1/S transition of the cell cycle. It depended on a binding site for the oncogenic transcription factor E2F located in the first exon of F-type mRNA. This effect was inhibited by agents that increase cAMP concentration. The data provide the first evidence that a gene involved in the control of glycolysis can be regulated by a late-serum-response promoter in an E2F-dependent way.