A novel factor binding to the glucose response elements of liver pyruvate kinase and fatty acid synthase genes.
Transcription of the liver type pyruvate kinase and lipogenesis enzyme genes is induced by high carbohydrate in liver. We have found a novel protein factor in rat liver nuclei that binds to the glucose response element (CACGTG motifs) of the pyruvate kinase gene (Liu, Z. , Thompson, K. S., and Towle, H. C. (1993) J. Biol. Chem. 268, 12787-12795) and the "insulin response element" of fatty acid synthase gene. The amounts of this DNA-binding protein, termed "glucose response element binding protein" (GRBP) in the nuclear extract, were increased in liver by a high carbohydrate diet and decreased by starvation, 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 thermal inactivation than the latter. Kinetics of glucose activation of the cytosolic GRBP in a primary culture of hepatocytes indicated that a half-maximum activation was achieved after 6 h, and glucose concentration required for the maximum activation of the GRBP was approximately 12 mM. Dibutyryl-cAMP, 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.
Hasegawa
J
J
Research and Development, Dallas Veterans Affairs Medical Center and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75216, USA.
Osatomi
K
K
Wu
R F
RF
Uyeda
K
K
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D064429:Fatty Acid Synthases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D019319:Okadaic Acid / Q000494:pharmacology; D011770:Pyruvate Kinase / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D004268:DNA-Binding Proteins; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005576:Colforsin; D019319:Okadaic Acid; D000242:Cyclic AMP; D064429:Fatty Acid Synthases; D011770:Pyruvate Kinase; D005947:Glucose