Allosteric effects govern nuclear receptor action: DNA appears as a player.
Fiche publication
Date publication
janvier 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
Tous les auteurs :
Gronemeyer H, Bourguet W
Lien Pubmed
Résumé
Nuclear receptors (NRs) are a family of transcription factors that regulate cognate gene networks, resulting in profound physiological and pathophysiological changes. Dysfunctional NR signaling leads to proliferative, reproductive, and metabolic diseases such as cancer, infertility, obesity, or diabetes. Indeed, NR-based pharmaceuticals are among the most commonly used drugs. NRs function by communicating with the intracellular and extracellular environment, thereby both sensing and modulating the status of cells. They respond to incoming signals by orchestrating transcriptional as well as nongenomic effects. They do so through an ability to respond to various effectors, such as the cognate ligand, by allosteric structural alterations that are the basis of further signal propagation. A mechanism has now been revealed by which DNA could act as an allosteric effector to modulate glucocorticoid receptor activity. This is a new regulatory paradigm for NR action that may help to explain how a receptor fine-tunes its target gene network.
Référence
Sci Signal. 2009 Jun 2;2(73):pe34.