A novel factor finding to the glucose response elements of liver pyruvate kinase and fatty acid synthase genes

Transcription of the liver type pyruvate kinase and lipogenesis enzyme gene s is induced by high carbohydrate in liver. We have found a novel protein f actor in rat Liver nuclei that binds to the glucose response element (CACGT G motifs) of the pyruvate kinase gene (Liu, Z., Thompson, & S., and Towle, H. C. (1993) J. Biol Chem. 268,12787-12795) and the "insulin response eleme nt" of fatty acid synthase gene. The amounts of this DNA-binding protein, t ermed "glucose response element binding protein" (GRBP) in the nuclear extr act, were increased in liver by a high carbohydrate diet and decreased by s tarvation, high fat, and high protein diet. GRBP also occurs in cytosols of liver and is dependent on carbohydrate. Both the nuclear and the cytosolic GRBP showed similar properties, except the former was more resistant to th ermal inactivation than the latter. Kinetics of glucose activation of the c ytosolic GRBP in a primary culture of hepatocytes indicated that a half-max imum activation was achieved after 6 h, and glucose concentration required for the maximum activation of the GRBP was approximately 12 mM. Dibutyryl-c AMP, okadaic acid, and forskolin inhibited glucose activation of both GRBP and liver pyruvate kinase transcription. These results suggested that GRBP may be a factor that recognizes the glucose response motif site and may be involved in mediating carbohydrate response of the pyruvate kinase gene.