Involvement of {beta}-catenin and unusual behavior of CBP and p300 in glucocorticosteroid signaling in Schwann cells.

Abstract:

:In the nervous system, glucocorticosteroid hormones play a major role during development and adult life. Myelin-forming cells are among the targets of glucocorticosteroids, which have been shown to promote myelination both in the central and peripheral nervous system. Glucocorticosteroid-stimulated gene transcription is mediated by the glucocorticosteroid receptor (GR) that recruits coactivators of the p160 family, forming a docking platform for secondary coactivators, such as cAMP-response element binding protein (CREB)-binding protein (CBP) or its close homologue, p300. Here, we investigated the role of CBP and p300 in mouse Schwann cells (MSC80). We show that, although the CBP/p300 binding domain of steroid receptor coactivator-1 is crucial for GR transactivation, neither CBP nor p300 enhanced GR transcriptional activation, as shown by overexpression and small interfering RNA (siRNA) knocking-down experiments. Unexpectedly, overexpression of p300, considered as a coactivator of the GR, resulted in inhibition of GR transcriptional activity. Studies with p300 deletion mutants demonstrated that p300-dependent repression is related to its acetyltransferase activity. Functional and pull-down assays showed that beta-catenin may be the coactivator replacing CBP in the GR transcriptional complex. Our results suggest the formation of a GR-coactivator complex within Schwann cells, indicating that glucocorticosteroids may act by means of unusual partners in the nervous system, and we show a repressive effect of p300 on nuclear receptors.

authors

Fonte C,Grenier J,Trousson A,Chauchereau A,Lahuna O,Baulieu EE,Schumacher M,Massaad C

doi

10.1073/pnas.0506930102

keywords:

subject

Has Abstract

pub_date

2005-10-04 00:00:00

pages

14260-5

issue

40

eissn

0027-8424

issn

1091-6490

pii

0506930102

journal_volume

102

pub_type

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