Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 2 June 2009
Vol. 2, Issue 73, p. pe34
[DOI: 10.1126/scisignal.273pe34]


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

Hinrich Gronemeyer1* and William Bourguet2*

1 Department of Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), BP 10142, 67404 Illkirch Cedex, C. U. de Strasbourg, France.
2 INSERM U554, 34090 Montpellier, France; CNRS UMR5048, 34090 Montpellier, France; Centre de Biochimie Structurale, Université Montpellier 1 et 2, 34090 Montpellier, France.

Abstract: 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.

* Corresponding authors. E-mail, hg{at} (H.G.); bourguet{at} (W.B.)

Citation: H. Gronemeyer, W. Bourguet, Allosteric Effects Govern Nuclear Receptor Action: DNA Appears as a Player. Sci. Signal. 2, pe34 (2009).

Read the Full Text

In-depth Proteomic Characterization of Endogenous Nuclear Receptors in Mouse Liver.
Q. Liu, C. Ding, W. Liu, L. Song, M. Liu, L. Qi, T. Fu, A. Malovannaya, Y. Wang, J. Qin, et al. (2013)
Mol. Cell. Proteomics 12, 473-484
   Abstract »    Full Text »    PDF »
In vitro DNA-binding profile of transcription factors: methods and new insights.
J. Wang, J. Lu, G. Gu, and Y. Liu (2011)
J. Endocrinol. 210, 15-27
   Abstract »    Full Text »    PDF »
Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin.
D. G. Ceschin, M. Walia, S. S. Wenk, C. Duboe, C. Gaudon, Y. Xiao, L. Fauquier, M. Sankar, L. Vandel, and H. Gronemeyer (2011)
Genes & Dev. 25, 1132-1146
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882