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This version published online on August 26, 2004
Molecular Endocrinology, doi:10.1210/me.2004-0241
Molecular Endocrinology Vol. 0, No. 2004 200402411-
doi:10.1210/me.2004-0241
Copyright © 2004 by the Endocrine Society.
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Submitted on June 14, 2004
Accepted on August 17, 2004

Selective recruitment of p160 coactivators on glucocorticoid-regulated promoters in Schwann cells

Julien Grenier, Amalia Trousson, Anne Chauchereau, Larbi Amazit, Audrey Lamirand, Philippe Leclerc, Anne Guiochon-Mantel, Michael Schumacher, and Charbel Massaad*

INSERM U488, IFR93, 80 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France; CNRS UPR 9079, 7 rue Guy Moquet, 94800 Villejuif, France; INSERM U135, Hôpital Bicêtre, AP-HP, IFR93, 94275 Le Kremlin-Bicêtre Cedex, France; Faculté de Médecine Paris-Sud, 63, rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France

* To whom correspondence should be addressed. E-mail: massaad{at}kb.inserm.fr.

In the nervous system, glucocorticoid hormones play a major role during development and throughout life. We studied the mechanisms of action of the glucocorticoid receptor (GR) and its interactions with p160 coactivator family members (SRC-1 (a and e), SRC-2 and SRC-3) in mouse Schwann cells (MSC80). We found that the three p160s were expressed in MSC80 cells. We have shown by functional overexpression and RNA interference experiments that the recruitment of these coactivators by the GR is promoter-dependent. A minimal promoter containing two Glucocorticoid Response Elements, (GRE)2-TATA, recruits SRC-1 (a and e) and SRC-3 whereas SRC-2 is excluded. Within the context of the more complex MMTV promoter, GR recruits SRC-1e and SRC-2 while SRC-1a and SRC-3 are not implicated. Furthermore, we have identified cytosolic aspartate aminotransferase (cAspAT) as a GR-target gene in MSC80 cells by microarray experiments. The GR recruits exclusively SRC-1e in the context of the cAspAT promoter. SRC-1 being the omnipresent coactivator of GR, we further investigated the interactions between GR and this coactivator in Schwann cells by reporter assays and immunocytochemistry experiments with deleted forms of SRC-1. We have shown that SRC-1 unexpectedly interacts with GR via its two nuclear receptor binding domains, thus, providing a novel mechanism of GR signaling within the nervous system.


Key words: Glucocorticoid receptor • SRC-1 • SRC-2 • SRC-3 • siRNA • coactivator • nucleocytoplasmic shuttling • Schwann cells

NURSA Molecule Pages Link:

Nuclear Receptors:   GR
Coregulators:   RIP140  |  SRC-1  |  GRIP1  |  AIB1
Ligands:   Dexamethasone  |  Progesterone



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