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Updated: Jul 25, 2026
11:07
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Expression level-dependent contribution of glucocorticoid receptor domains for functional interaction with STAT5
W Doppler1, M Windegger, C Soratroi
1Institut für Medizinische Chemie und Biochemie, Universität Innsbruck, A-6020 Innsbruck, Austria. Wolfgang.Doppler@uibk.ac.at
Molecular and Cellular Biology
|April 5, 2001
Summary
Glucocorticoid receptor (GR) action on beta-casein gene transcription depends on STAT5. GR concentration and DNA binding influence this synergy, with high GR levels enabling DNA-independent coactivation and drug responses.
Area of Science:
- Molecular Endocrinology
- Gene Regulation
- Transcription Factor Interaction
Background:
- Glucocorticoid receptor (GR) action on beta-casein gene transcription is a model for transcription factor synergy.
- GR activity is known to be dependent on STAT5, another key transcription factor.
Purpose of the Study:
- To investigate the domain requirements of GR for synergistic responses with STAT5.
- To explore how GR expression levels and specific domains affect transactivation of the beta-casein gene.
- To clarify the role of DNA binding in GR's coactivation function.
Main Methods:
- Transfection experiments using GR mutants in CV-1 or COS-7 cells.
- Analysis of GR domain requirements for STAT5-dependent transactivation.
- Assessment of antiglucocorticoid RU486 and dexamethasone activity at varying GR expression levels.
Main Results:
- At low GR expression, STAT5-dependent transactivation was impaired, and RU486 showed weak agonistic activity.
- Exchange of the GR N-terminal region reduced STAT5-dependent transactivation at both low and high expression levels.
- High GR expression enabled DNA-binding independent coactivation of STAT5 and potent RU486-mediated transcription.
Conclusions:
- GR's mode of action is influenced by promoter type and GR concentration.
- High GR expression levels allow for DNA-binding independent coactivation with STAT5.
- GR DNA binding is essential for beta-casein gene expression in mammary epithelial cells.
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