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The relationship between glucocorticoid receptor binding to Hsp90 and receptor function.
W B Pratt1, F C Dalman, S Meshinchi
1Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Nihon Naibunpi Gakkai Zasshi
|December 20, 1990
Summary
The heat shock protein 90 (hsp90) chaperone binds the glucocorticoid receptor (GR), regulating its DNA binding and steroid binding affinity. Hormone binding causes hsp90 dissociation, activating the GR.
Area of Science:
- Molecular Biology
- Cellular Biology
- Endocrinology
Background:
- The glucocorticoid receptor (GR) is a key regulator of gene expression.
- Hsp90 is a molecular chaperone involved in protein folding and function.
- The interaction between GR and hsp90 is crucial for GR activity.
Purpose of the Study:
- To summarize evidence on how hsp90 association influences GR functional states.
- To elucidate the role of hsp90 in GR's DNA binding and steroid binding.
- To compare GR's hsp90 dependence with other steroid receptors.
Main Methods:
- Review of existing literature on GR-hsp90 interactions.
- Analysis of GR functional states (DNA binding, steroid binding) in relation to hsp90.
- Comparison of GR behavior with thyroid hormone receptor.
Main Results:
- Hsp90 binding to GR represses DNA binding activity.
- Hsp90 association is required for high-affinity steroid binding by GR.
- Hormone binding induces hsp90 dissociation, activating GR for DNA binding and nuclear translocation.
- Unlike GR, the thyroid hormone receptor does not associate with hsp90 and binds DNA upon translation.
Conclusions:
- Hsp90 acts as a critical regulator of GR function, controlling its activity until hormone binding.
- The GR-hsp90 complex maintains GR in an inactive state, poised for activation.
- Understanding GR-hsp90 dynamics provides insights into steroid hormone signaling pathways.