Insulin potentiates the transactivation potency of the glucocorticoid receptor.
A single copy of a glucocorticoid-responsive element (GRE) is sufficient in mediating the combinatorial response of a promoter to both glucocorticoids and insulin in HepG2 cells. This requires the presence of active glucocorticoid receptor (GR) since the response is significantly inhibited by the anti-glucocorticoid RU30406. The N'- and C'-terminal parts of the GR protein are not involved in mediating the response. Insulin had no effect on GR binding to GRE but it affected both the level and the phosphorylation state of nuclear-bound GR. Thus, insulin alters the GR transactivation potency while, concomitantly, modifies the molecule at the posttranslational level.
Georgakopoulos
A
A
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Tsawdaroglou
N
N
D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D010957:Plasmids; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D007328:Insulin; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D015534:Trans-Activators; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase