Aluminum fluoride inhibition of glucocorticoid receptor inactivation and transformation
- Univ. of South Carolina School of Medicine, Columbia (USA)
Fluoride, in the presence of aluminum ions, reversibly inhibits the temperature-mediated inactivation of unoccupied glucocorticoid receptors in cytosol preparations from mouse L cells. The effect is concentration-dependent, with virtually complete stabilization of specific glucocorticoid-binding capacity at 2 mM fluoride and 100 microM aluminum. These concentrations of aluminum and fluoride are ineffective when used separately. Aluminum fluoride also stabilizes receptors toward inactivation by gel filtration and ammonium sulfate precipitation. Aluminum fluoride prevents temperature-dependent transformation of steroid-receptor complexes to the DNA-binding state. Aluminum fluoride does not inhibit calf intestine alkaline phosphatase, and unoccupied receptors inactivated by this enzyme in the presence of aluminum fluoride can be completely reactivated by dithiothreitol. The effects of aluminum fluoride are due to stabilization of the complex between the glucocorticoid receptor and the 90-kDa mammalian heat-shock protein hsp90, which suggests that aluminum fluoride interacts directly with the receptor. Endogenous thermal inactivation of receptors in cytosol is not accompanied by receptor dephosphorylation. However, inactivation is correlated with dissociation of hsp90 from the unoccupied receptor. These results support the proposal that hsp90 is required for the receptor to bind steroid and dissociation of hsp90 is sufficient to inactivate the unoccupied receptor.
- OSTI ID:
- 6693722
- Journal Information:
- Biochemistry; (USA), Vol. 29:14; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ALUMINIUM FLUORIDES
BIOLOGICAL EFFECTS
GLUCOCORTICOIDS
RECEPTORS
ANIMAL CELLS
BIOCHEMICAL REACTION KINETICS
CHROMATOGRAPHY
MICE
PHOSPHATES
THERMODYNAMICS
ADRENAL HORMONES
ALUMINIUM COMPOUNDS
ANIMALS
CORTICOSTEROIDS
FLUORIDES
FLUORINE COMPOUNDS
HALIDES
HALOGEN COMPOUNDS
HYDROXY COMPOUNDS
KETONES
KINETICS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
PREGNANES
PROTEINS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
STEROIDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology