Antagonism between Nur77 and Glucocorticoid Receptor for Control of Transcription

• DOI: 10.1128/mcb.17.10.5952
• Publication Date: 2015-10-09T22:09:44Z
• Authors: Alexandre Philips; Mario Maira; Alaka Mullick; Michel Chamberland; Sylvie Lesage; Patrice Hugo; Jacques Drouin
• Keywords: 0301 basic medicine; Receptors, Steroid; Hybridomas; Pro-Opiomelanocortin; Corticotropin-Releasing Hormone; DNA, Recombinant; Receptors, Antigen, T-Cell; Receptors, Cytoplasmic and Nuclear; DNA; Dexamethasone; Cell Line; 3. Good health; DNA-Binding Proteins; Mice; 03 medical and health sciences; Receptors, Glucocorticoid; Pituitary Gland; Nuclear Receptor Subfamily 4, Group A, Member 1; Animals; RNA, Messenger; Promoter Regions, Genetic; Glucocorticoids; Signal Transduction

Two important functions of glucocorticoids (Gc), namely, suppression immune system function and feedback repression the hypothalamo-pituitary-adrenal (HPA) axis, are mediated through gene transcription. Previous studies have indicated that this is exerted in part antagonism between glucocorticoid receptors (GR) AP-1 family transcription factors. However, mechanism could not account for pro-opiomelanocortin (POMC) gene, an regulator HPA axis. Our recent identification orphan nuclear receptor Nur77 as a mediator CRH induction POMC led us, present work, to show Gc antagonize positive signal at two levels. First, partly blunt mRNA, second, they Nur77-dependent GR by action on NurRE element gene. activity was observed response physiological stimuli both endocrine (CRH POMC) lymphoid (T-cell activation) cells. In transfection experiments, transcriptional activation repressor liganded titrated each other their cognate DNA target. vitro binding experiments well mutation analysis suggest very similar AP-1. The convergence signals (and also probably related members) negative appears be general control transcription, since it active