Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids.
The phosphoenolpyruvate carboxykinase (PEPCK) gene encodes the rate-limiting enzyme in gluconeogenesis. Glucocorticoids enhance PEPCK gene expression through a multicomponent regulatory complex. We show that a full response to glucocorticoids requires two DNA segments: 1) a glucocorticoid response unit (GRU), centered at about position -400, which contains two accessory factor elements (AF1 and AF2) and two glucocorticoid receptor binding sites (GR1 and GR2), and 2) a basal promoter/cyclic AMP response element (E/CRE) at about position -90, which binds the transcription factor CREB. A protein-protein interaction was observed in vitro between GR and CREB that might account for the role of the E/CRE in the glucocorticoid response of the PEPCK gene.
Imai
E
E
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-0615.
Miner
J N
JN
Mitchell
J A
JA
Yamamoto
K R
KR
Granner
D K
DK
D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004277:DNA, Single-Stranded; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004277:DNA, Single-Stranded; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D010729:Phosphoenolpyruvate Carboxykinase (GTP)