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Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones¹

Department of Pharmacology (W.B.P.), The University of Michigan Medical School, Ann Arbor, Michigan 48109; and Department of Biochemistry and Molecular Biology (D.O.T.), Mayo Graduate School, Rochester, Minnesota 55905

I. Introduction

II. 9S Receptors

A. Estrogen receptors (ERs)

B. Progesterone receptors (PRs)

C. Androgen receptors (ARs)

D. Glucocorticoid receptors (GRs)

E. Mineralocorticoid receptors (MRs)

F. Dioxin receptors (DRs)

G. Antheridiol receptors

III. Receptor Transformation

A. Transformed receptors bind polyanions

B. Artifactual transforming conditions

C. Models of cytosolic receptor transformation

D. Physiological relevance of receptor transformation before the discovery of hsp90 binding

IV. Molybdate Stabilization of Receptors

A. Stabilization of steroid binding activity

B. Inhibition of transformation

C. Mechanism of molybdate stabilization

V. Purification of Untransformed Receptors Leads to hsp90

A. The untransformed receptor is a heterocomplex

B. Antibodies against the 90-kDa protein

C. The 90-kDa receptor-associated protein is hsp90

VI. Role of hsp90 in Receptor Function

A. General properties of hsp90

B. Stoichiometry of receptor·hsp90 complex

C. hsp90 Binds to the receptor HBD

D. Region of hsp90 that binds receptor

E. Requirement of hsp90 for steroid binding

F. Receptor transformation and hsp90 dissociation

G. Receptor inactivation by hsp90

H. Evidence that hsp90 is a physiologically significant regulator of receptor function

I. Potential roles of hsp90 in receptor turnover and trafficking

VII. Other Proteins Recovered in Native Receptor Heterocomplexes

A. hsp70

B. p23

C. Immunophilins

VIII. The Receptor Heterocomplex Assembly Mechanism

A. The receptor·hsp90 heterocomplex assembly activity in reticulocyte lysate

B. Components of the heterocomplex assembly system

C. Effect of geldanamycin on heterocomplex assembly

D. The concept of a dynamic heterocomplex assembly machine

E. Heterocomplex assembly with hsp90 is a very basic and conserved process

IX. Other Proteins That Are Bound to hsp90

X. Summary