Abstract
We have identified a new first step in the hormonal activation of the glucocorticoid receptor (GR). Rather than causing immediate dissociation of the cytoplasmic GR heterocomplex, binding of hormone-induced substitution of one immunophilin (FKBP51) for another (FKBP52), and concomitant recruitment of the transport protein dynein while leaving Hsp90 unchanged. Immunofluorescence and fractionation revealed hormone-induced translocation of the hormone-generated GR-Hsp90-FKBP52-dynein complex from cytoplasm to nucleus, a step that precedes dissociation of the complex within the nucleus and conversion of GR to the DNA-binding form. Taken as a whole, these studies identify immunophilin interchange as the earliest known event in steroid receptor signaling and provide the first evidence of differential roles for FKBP51 and FKBP52 immunophilins in the control of steroid receptor subcellular localization and transport.
Highlights
We have identified a new first step in the hormonal activation of the glucocorticoid receptor (GR)
We have identified a new first step in hormonal activation of steroid receptors, i.e. hormone-induced switching of FKBP51 and FKBP52 within the complex, showing that this event leads to movement of the newly generated complex to the nucleus prior to its final dissociation
The results show almost no GR-associated FKBP52 in the absence of Dex but a large increase in FKBP52 for the hormone-bound receptor
Summary
HORMONE-INDUCED SWITCHING OF FKBP51 AND FKBP52 IMMUNOPHILINS Todd H. Alerts: When this article is cited When a correction for this article is posted. This article cites 23 references, 15 of which can be accessed free at http://www.jbc.org/content/277/7/4597.full.html#ref-list-1
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