Τόμος 18 (2004) – Τεύχος 2 – Άρθρο 5 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 18 (2004) – Issue 2 – Article 5 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title Control of glucocorticoid receptor signaling by heat shock proteins
Authors Michael N. Alexis, Dimitra J. Mitsiou, Despina Siriani and Ida Florentin

Molecular Endocrinology Programme, Institute of Biological Research and Biotechnology, The National Hellenic Research Foundation, 48, Vas. Constantinou Ave, 11635, Athens, Greece.

Citation Alexis, M.N., Mitsiou, D.J., Siriani, D., Florentin, I.: Control of glucocorticoid receptor signaling by heat shock proteins, Epitheorese Klin. Farmakol. Farmakokinet. 18(2): 212-216 (2004)
Publication Date Accepted for publication: 2004
Full Text Language English
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Summary Glucocorticoid receptor regulation of gene expression is thought to depend on Hsp70-driven continuous reactivation of a spontaneously inactivated hormone-responsive state. Since Hsp70 appears to be titrated in cells that transiently overexpress the receptor, assembly intermediates may accumulate when more receptor is produced than can be assembled to hormone-responsive complex. Our data support the presence in such cells of non-hormone-binding nuclear receptor forms possessing constitutive DNA-binding activity and capable of repressing hormone-activated transcription. Hsp70 is also titrared in cells undergoing heat shock. Our data argue that receptor activity is maintained in heat-shocked cells, provided that denaturation and/or aggregation of the receptor is prevented by Hsp70; and that the concentration of the chaperone is the limiting determinant of receptor activity. With respect to Hsp90, our data indicate that by cycling between high and low-affinity receptor interactive states by ATP binding and hydrolysis to ADP, this chaperone may decide between receptor refolding and degradation depending on the metabolic potential of the cell.
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10.  Mitsiou D.J., Siriani D., Katsanou E.S., Florentin I., Georgakopoulos A., Alexis M.N.: Maintenance of glucocorticoid receptor function following severe heat-shock of heat- conditioned cells. Mol. Cell Endocrinol. 201: 97-10 (2003)

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