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

Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14260-5. doi: 10.1073/pnas.0506930102. Epub 2005 Sep 26.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CREB-Binding Protein / metabolism*
  • Gene Expression Regulation*
  • Glucocorticoids / metabolism*
  • Immunohistochemistry
  • Luciferases
  • Mice
  • RNA, Small Interfering / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Schwann Cells / metabolism*
  • Signal Transduction / physiology*
  • Transfection
  • beta Catenin / metabolism*
  • p300-CBP Transcription Factors / metabolism*


  • Glucocorticoids
  • RNA, Small Interfering
  • Receptors, Glucocorticoid
  • beta Catenin
  • Luciferases
  • CREB-Binding Protein
  • p300-CBP Transcription Factors