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Scientific article
English

The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo

Contributors

Riggs, Daniel L.; Roberts, Patricia J.; Chirillo, Samantha C.; Cheung-Flynn, Joyce; Prapapanich, Viravan; Ratajczak, Thomas; Gaber, Richard; Picard, Didier; Smith, David F.

Published in

EMBO journal, vol. 22, no. 5, p. 1158-1167

Publication date

2003

Abstract

Hsp90 is required for the normal activity of steroid receptors, and in steroid receptor complexes it is typically bound to one of the immunophilin-related co-chaperones: the peptidylprolyl isomerases FKBP51, FKBP52 or CyP40, or the protein phosphatase PP5. The physiological roles of the immunophilins in regulating steroid receptor function have not been well defined, and so we examined in vivo the influences of immunophilins on hormone-dependent gene activation in the Saccharomyces cerevisiae model for glucocorticoid receptor (GR) function. FKBP52 selectively potentiates hormone-dependent reporter gene activation by as much as 20-fold at limiting hormone concentrations, and this potentiation is readily blocked by co-expression of the closely related FKBP51. The mechanism for potentiation is an increase in GR hormone-binding affinity that requires both the Hsp90-binding ability and the prolyl isomerase activity of FKBP52.

Keywords

  • Animals
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Genes, Reporter
  • Glucocorticoids/metabolism
  • HSP90 Heat-Shock Proteins/metabolism
  • Humans
  • Models, Molecular
  • Molecular Chaperones/genetics/metabolism
  • Peptidylprolyl Isomerase/metabolism
  • Protein Binding
  • Protein Conformation
  • Receptors, Glucocorticoid/metabolism
  • Saccharomyces cerevisiae/physiology
  • Signal Transduction/physiology
  • Tacrolimus Binding Proteins/metabolism
  • Transcriptional Activation

UNIGE affiliation entities

Citation (ISO format)

RIGGS, Daniel L. et al. The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. In: EMBO journal, 2003, vol. 22, n° 5, p. 1158–1167. doi: 10.1093/emboj/cdg108

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0261-4189
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Technical informations

Creation

04/12/2009 13:36:00

First validation

04/12/2009 13:36:00

Update

14/03/2023 15:19:28

Status update

14/03/2023 15:19:28

Last indexation

29/10/2024 12:46:55
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