Selective recruitment of p160 coactivators on glucocorticoid-regulated promoters in Schwann cells.
Julien Grenier
(1, 2)
,
Amalia Trousson
(1, 2)
,
Anne Chauchereau
(3)
,
Larbi Amazit
(4)
,
Audrey Lamirand
,
Philippe Leclerc
(5)
,
Anne Guiochon-Mantel
(4, 6)
,
Michael Schumacher
(1, 2)
,
Charbel Massaad
(1, 2)
1
Stéroïdes et système nerveux : physiopathologie moléculaire et clinique
2 Faculté de Médecine Paris-Sud
3 GO - UMR 8125 - Génétique oncologique
4 Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique
5 IFR de Bicêtre
6 Service de génétique moléculaire, pharmacogénétique et hormonologie
2 Faculté de Médecine Paris-Sud
3 GO - UMR 8125 - Génétique oncologique
4 Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique
5 IFR de Bicêtre
6 Service de génétique moléculaire, pharmacogénétique et hormonologie
Julien Grenier
- Fonction : Auteur
- PersonId : 1395986
- IdHAL : julien-grenier
Audrey Lamirand
- Fonction : Auteur
Anne Guiochon-Mantel
- Fonction : Auteur
- PersonId : 1321977
- IdHAL : anne-guiochon-mantel
- ORCID : 0000-0003-1737-1409
Résumé
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 [steroid receptor coactivator (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 mouse mammary tumor virus promoter, GR recruits SRC-1e and SRC-2, whereas SRC-1a and SRC-3 are not implicated. Furthermore, we have identified cytosolic aspartate aminotransferase as a GR target gene in MSC80 cells by microarray experiments. The GR recruits exclusively SRC-1e in the context of the cytosolic aspartate aminotransferase promoter. Because SRC-1 is 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.
Format du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Selective recruitment of p160 coactivators on glucocorticoid-regulated promoters in Schwann cells.
|
Résumé |
en
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 [steroid receptor coactivator (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 mouse mammary tumor virus promoter, GR recruits SRC-1e and SRC-2, whereas SRC-1a and SRC-3 are not implicated. Furthermore, we have identified cytosolic aspartate aminotransferase as a GR target gene in MSC80 cells by microarray experiments. The GR recruits exclusively SRC-1e in the context of the cytosolic aspartate aminotransferase promoter. Because SRC-1 is 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.
|
Auteur(s) |
Julien Grenier
1, 2
, Amalia Trousson
1, 2
, Anne Chauchereau
3
, Larbi Amazit
4
, Audrey Lamirand
, Philippe Leclerc
5
, Anne Guiochon-Mantel
4, 6
, Michael Schumacher
1, 2
, Charbel Massaad
1, 2
1
Stéroïdes et système nerveux : physiopathologie moléculaire et clinique
( 27915 )
- Bat Gregory Pincus 80 rue du Général Leclerc 94276 Le Kremlin Bicêtre
- France
2
Faculté de Médecine Paris-Sud
( 7220 )
- 63 rue Gabriel Péri 94270 Le Kremlin-Bicêtre cedex
- France
3
GO - UMR 8125 -
Génétique oncologique
( 1269 )
- Gustave Roussy. Pavillon de recherche 1. 114, rue Édouard-Vaillant 94805 Villejuif Cedex -France
- France
4
Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique
( 3051 )
- Faculté de médecine 63, Rue Gabriel Peri 94276 LE KREMLIN BICETRE
- France
5
IFR de Bicêtre
( 2767 )
- Batiment Inserm Gregory Pincus PARIS XI 80, Rue du General Leclerc 94276 LE KREMLIN BICETRE CEDEX
- France
6
Service de génétique moléculaire, pharmacogénétique et hormonologie
( 31680 )
- 78, rue du Général Leclerc 94275 Le Kremlin Bicêtre
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2004-12
|
Volume |
18
|
Numéro |
12
|
Page/Identifiant |
2866–79
|
Domaine(s) |
|
DOI | 10.1210/me.2004-0241 |
Pubmed Id | 15331759 |
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