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. (C) 1998 Elsevier Science Ltd. All rights reserved.