Hormone response of rodent phenylalanine hydroxylase requires HNF1 and the glucocorticoid receptor.
Expression of the rodent phenylalanine hydroxylase (PAH) gene is dependent upon hormones. Induction by glucocorticoids and cAMP occurs slowly and maximal stimulation is obtained by a synergistic effect of the two compounds. Hormone responsiveness is conferred by the tissue-specific HSIII enhancer and involves (i) protein kinase A mediating the cAMP response, even though a consensus sequence for binding of the cAMP response element binding protein is not present; (ii) other serine/threonine kinases as deduced from inhibitor studies; (iii) glucocorticoid receptor protein bound to glucocorticoid response element half sites; and (iv) binding of the liver-enriched transcription factor hepatocyte nuclear factor 1 (HNF1) to sites in the enhancer. Glucocorticoid receptor and HNF1, bound to their cognate sites, cooperatively increase the glucocorticoid response of the PAH gene, this response being synergistically enhanced by cAMP after long-term treatment.
Bristeau
A
A
Unité de Génétique de la Différenciation, FRE 2364, Centre National de la Recherche Scientifique, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Catherin
A M
AM
Weiss
M C
MC
Faust
D M
DM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000494:pharmacology; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010651:Phenylalanine Hydroxylase / Q000235:genetics / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D007211:Indoles; D008301:Maleimides; D009687:Nuclear Proteins; D010726:Phosphodiesterase Inhibitors; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D019319:Okadaic Acid; D003907:Dexamethasone; D000242:Cyclic AMP; D010651:Phenylalanine Hydroxylase; D017868:Cyclic AMP-Dependent Protein Kinases; C070515:bisindolylmaleimide I; D015056:1-Methyl-3-isobutylxanthine