Novel mechanism of action for Nur77 and antagonism by glucocorticoids: a convergent mechanism for CRH activation and glucocorticoid repression of POMC gene transcription.
Whereas orphan nuclear receptors of the Nur77 (NGFI-B) subfamily were previously known to act on transcription as monomers or as heterodimers with RXR, we have recently shown that Nur77 homodimers potently activate transcription upon interaction with a novel palindromic response element, the NurRE. In fact, reporter plasmids containing the NurRE respond to physiological stimuli in conditions where the NBRE, a binding site for Nur77 monomers, does not. Nur77 and its related receptors were shown to be important mediators for control of apoptosis induced by the T-cell receptor, and they also mediate the effect of the hypothalamic hormone CRH on transcription of the pituitary pro-opiomelanocotin (POMC) gene. In both systems, glucocorticoids antagonize the stimulatory effects of Nur77 on transcription by a mechanism that involves protein:protein interactions. Thus, the Nur77 signalling pathway appears to be a point of convergence for stimulatory signals and glucocorticoid repression in both endocrine and lymphoid systems.
Laboratoire de génétique moléculaire, Institut de recherches cliniques de Montréal, Que., Canada. drouinj@ircm.umontreal.ca
J
J
Drouin
M
M
Maira
A
A
Philips
D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D019281:Dimerization; D004703:Endocrine System / Q000378:metabolism; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone