Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5.
Molecular and Cellular Neuroscience. 2017-07-01; 82: 96-104
DOI: 10.1016/j.mcn.2017.05.001
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1. Mol Cell Neurosci. 2017 Jul;82:96-104. doi: 10.1016/j.mcn.2017.05.001. Epub 2017
May 3.
Retinoic acid increases glucocorticoid receptor phosphorylation via
cyclin-dependent kinase 5.
Brossaud J(1), Roumes H(2), Helbling JC(2), Moisan MP(2), Pallet V(2), Ferreira
G(2), Biyong EF(2), Redonnet A(2), Corcuff JB(3).
Author information:
(1)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, F-33076 Bordeaux, France;
Departments of Nuclear Medicine University Hospital and University of Bordeaux,
France. Electronic address: .
(2)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, F-33076 Bordeaux, France.
(3)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, F-33076 Bordeaux, France;
Departments of Nuclear Medicine University Hospital and University of Bordeaux,
France.
Glucocorticoid receptor (GR) function is modulated by phosphorylation. As
retinoic acid (RA) can activate some cytoplasmic kinases able to phosphorylate
GR, we investigated whether RA could modulate GR phosphorylation in neuronal
cells in a context of long-term glucocorticoid exposure. A 4-day treatment of
dexamethasone (Dex) plus RA, showed that RA potentiated the (Dex)-induced
phosphorylation on GR Serine 220 (pSer220GR) in the nucleus of a hippocampal HT22
cell line. This treatment increased the cytoplasmic ratio of p35/p25 proteins,
which are major CDK5 cofactors. Roscovitine, a pharmacological CDK5 inhibitor, or
a siRNA against CDK5 prevented RA potentiation of GR phosphorylation.
Furthermore, roscovitine counter-acted the effect of RA on GR sensitive target
proteins such as BDNF or tissue-transglutaminase. These data help understanding
the interaction between RA- and glucocorticoid-signalling pathways, both of which
have strong influences on the adult brain.
Copyright © 2017 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.mcn.2017.05.001
PMID: 28477983 [Indexed for MEDLINE]