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Allosteric Effects Govern Nuclear Receptor Action: DNA Appears as a Player

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.

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Resource Type: Bibliography, Diagram, Illustration, Journal article/Issue, Review
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright

Authors and Editors: Hinrich Gronemeyer of Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Strasbourg, William Bourguet of Centre de Biochimie Structurale, Universite Montpellier
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes


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