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Updated: Aug 9, 2026
11:07
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Chaperoning of glucocorticoid receptors
W B Pratt1, Y Morishima, M Murphy
1Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Handbook of Experimental Pharmacology
|April 14, 2006
Summary
The Hsp90/Hsp70 chaperone machinery regulates glucocorticoid receptor (GR) function from steroid binding to degradation. This system is crucial for GR nuclear transport, transcriptional regulation, and turnover, ensuring proper cellular response.
Area of Science:
- Molecular Biology
- Cell Biology
- Protein Biochemistry
Background:
- The glucocorticoid receptor (GR) is a key regulator of cellular processes, and its function is tightly controlled.
- A complex chaperone machinery involving Hsp90 and Hsp70 proteins governs the GR's lifecycle.
Purpose of the Study:
- To elucidate the role of the Hsp90/Hsp70 chaperone machinery in the regulation of glucocorticoid receptor (GR) function.
- To investigate the mechanisms by which chaperones control GR steroid binding, nuclear translocation, transcriptional activity, and degradation.
Main Methods:
- The study focuses on the interactions between Hsp90, Hsp70, and the GR, examining ATP-dependent processes.
- Investigated the role of co-chaperones like Hop, Hsp40, and p23 in complex assembly.
- Analyzed GR translocation to the nucleus and its interaction with transcription sites.
Main Results:
- The Hsp90/Hsp70 machinery facilitates GR steroid binding by opening the ligand-binding cleft.
- Steroid binding induces GR conformational changes, promoting dynamic interactions with Hsp90 for nuclear translocation.
- The chaperone machinery is essential for GR nuclear localization, transcriptional regulation, and degradation via ubiquitylation.
Conclusions:
- The Hsp90/Hsp70 chaperone system acts as a comprehensive regulator ('cradle-to-grave') for the glucocorticoid receptor.
- Hsp70 plays a critical role in determining the fate of GR, directing it towards either functional complex assembly or degradation.
- This chaperone-mediated regulation is conserved across eukaryotes, highlighting its fundamental importance in cellular signaling.
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