Identification of a Sequence in the PEPCK Gene That Mediates a Negative Effect of Insulin on Transcription

• Published in: Science (American Association for the Advancement of Science) Vol. 249; no. 4968; pp. 533 - 537
• Main Authors: O'Brien, Richard M., Lucas, Peter C., Forest, Claude D., Magnuson, Mark A., Granner, Daryl K.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 03.08.1990; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Analysis; Animals; Base Sequence; Biochemistry; Biological and medical sciences; Cell Line; Cell lines; Cellular biology; Chloramphenicol O-Acetyltransferase - genetics; Chloramphenicol O-Acetyltransferase - metabolism; Cyclic AMP - analogs & derivatives; Cyclic AMP - physiology; Dexamethasone - pharmacology; DNA; Fundamental and applied biological sciences. Psychology; Gels; Genes; Genes, Regulator; Genetic mutation; Genetic regulation; Genetic transcription; Genetics; HEK293 cells; Insulin; Insulin - pharmacology; Insulin resistance; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nucleotide sequence; Phosphoenolpyruvate Carboxykinase (GTP) - genetics; Phosphoenolpyruvate Carboxykinase (GTP) - metabolism; Physiological aspects; Promoter regions; Recombinant Fusion Proteins - metabolism; Regulation; RNA, Messenger - drug effects; RNA, Messenger - genetics; Thionucleotides; Transcription (Genetics); Transcription, Genetic - drug effects; Transcription. Transcription factor. Splicing. Rna processing; Transfection; Ligand binding; Regulation(control); Transfection; Nucleotide sequence; Transcription; Cyclic AMP; Molecular interaction; Gene expression; Glucocorticoid; Insulin; Vector
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2166335

Phosphoenolpyruvate carboxykinase (PEPCK) governs the rate-limiting step in gluconeogenesis. Glucocorticoids and adenosine 3′,5′-monophosphate (cAMP) increase PEPCK gene transcription and gluconeogenesis, whereas insulin has the opposite effect. Insulin is dominant, since it prevents cAMP and glucocorticoid-stimulated transcription. Glucocorticoid and cAMP response elements have been located in the PEPCK gene and now a 15-base pair insulin-responsive sequence (IRS) is described. Evidence for a binding activity that recognizes this sequence is presented.