Opposite effects of CBP and p300 in glucocorticoid signaling in astrocytes.
In the nervous system, glucocorticoid hormones play a major role during development, and they continue to affect functional and structural plasticity throughout life. Glucocorticoid actions are mediated by their cognate nuclear receptor, the glucocorticoid receptor (GR). The transcriptional activity of the GR is enhanced by the recruitment of one of the transcriptional coactivators of the p160 family (SRCs), which are a docking platform for secondary coactivators like CBP, or its close homologue p300. Here, we investigated the implication of CBP and p300 coactivators in glial cells of the central and peripheral nervous system, namely in primary cultures of astrocytes and in Schwann cells. We show that both coregulators behave differently in either cell type. CBP enhances GR transcriptional activation in astrocytes, and has no effect in Schwann cells, whereas p300 exerts an inhibitory effect in both glial cells. Studies with p300 deletion mutants show that the repressive capacity of p300 is related to its acetyltransferase activity. This work shows striking differences between CBP and p300 actions in astrocytes. Moreover, in astrocytes the opposite effects of CBP and p300 could lead to a balance in the transactivation potency of the GR, in order to fine tune the action of glucocorticoids.
Fonte
Cosima
C
INSERM UMR788, University Paris-Sud (Paris XI), 80 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.
Trousson
Amalia
A
Grenier
Julien
J
Schumacher
Michael
M
Massaad
Charbel
C
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
D008565:Membrane Proteins; C408142:Pag1 protein, rat; D010750:Phosphoproteins; D011965:Receptors, Glucocorticoid; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat