ECE2015 Guided Posters Pituitary–Neuroendocrinology and central salt regulation (9 abstracts)
Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5
Hélène Roumes 1 , Julie Brossaud 1, , Aloïs Lemelletier 1 , Marie-Pierre Moisan 1 , Véronique Pallet 1 , Anabelle Redonnet 1 & Jean-Benoît Corcuff 1,
1UMR1286 INRA Univ Bordeaux, Bordeaux, France; 2University hospital, Bordeaux, France.
Background: According to the literature, glucocorticoid receptor (GR) function is modulated by phosphorylation. Retinoic acid (RA) can activate some cytoplasmic kinases able to phosphorylate GR.
Aim: As RA and glucocorticoids interact in neuronal cells, we investigated whether RA could modulate GR phosphorylation in such cells.
Methods: HT-22 hippocampal cells were cultured 4d with or without dexamethasone (Dex, 10-6 M) or RA (10-6 M). Western blots were either performed on total cell extracts or cytosolic and nuclear fractions.
Results: Indeed, a 4 d treatment by RA decreased the nuclear expression of GR phosphorylated on Serine 220 (pSer220GR). Conversely, RA increased Dex-dependent nuclear pSer220GR expression in HT22 cells. This treatment by RA had no effect on cyclin-dependent kinase 5 (CDK5) expression but increased the expression of p35 a major CDK5 cofactor. In the nucleus, roscovitine, a CDK5 inhibitor, suppressed the RA-dependent increase of the Dex-induced pSer220GR expression. Furthermore, roscovitine altered RA-dependent decrease of GR-induced transcriptional activity when using either a reporter gene with GR response elements or GR sensitive genes such as BDNF or tissue transglutaminase.
Conclusion: This study demonstrates that RA modulates GC signalling by increasing Ser220GR phosphorylation through at least a modulation of CDK5/p35 activity with an increase of cytoplasmic p35/p25 ratio. This study supports the idea that GR phosphorylation depends on the cellular environment aside from the presence of GR ligands.
Disclosure: This study was supported by the Conseil Régional d’Aquitaine and the University of Bordeaux1.
Volume 37
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Endocrine Abstracts
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