Glucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distribution

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dc.contributor.authorRobertson, Steven
dc.contributor.authorHapgood, Janet P.
dc.contributor.authorLouw, Ann
dc.date.accessioned2013-06-18T08:02:27Z
dc.date.available2014-03-03T03:00:03Z
dc.date.issued2013-02
dc.descriptionThe original publication is available at http://www.journals.elsevier.com/steroids/en_ZA
dc.description.abstractGlucocorticoid receptor (GR) concentrations and the ability of the GR to dimerize are factors which influence sensitivity to glucocorticoids. Upon glucocorticoid binding, the GR is actively transported into the nucleus, a crucial step in determining GR function. We examined the effects of GR concentration and the ability to dimerize on GR nuclear import, export and nuclear distribution using both live cell microscopy of GFP-tagged GR and immunofluorescence of untagged GR, with both wild type GR (GRwt) and dimerization deficient GR (GRdim). We found that the observed rate of GR nuclear import increases significantly at higher GR concentrations, at saturating concentrations of dexamethasone (10¯ 6 M) using GFP-tagged GR, while with untagged GR it is only discernable at sub-saturating ligand concentrations (10 ¯10 -10 ¯ 9 M). Loss of dimerization results in a slower observed rate of nuclear import (2.5- to 3.3-fold decrease for GFP-GRdim) as well as a decreased extent of GR nuclear localization (18–27% decrease for untagged GRdim). These results were linked to an increased rate of GR export at low GR concentrations (1.4- to 1.6-fold increase for untagged GR) and where GR dimerization is abrogated (1.5- to 1.7-fold increase for GFP-GRdim). Furthermore, GR dimerization was shown to be required for the appearance of discrete GC-dependent GR nuclear foci, the loss of which may explain the increased rate of GR export for the GRdim. The reduction in the observed rate of nuclear import and increased rate of nuclear export displayed at low GR concentrations and by the GRdim could explain the lowered glucocorticoid response under these conditions.en_ZA
dc.description.versionPost-printen_ZA
dc.embargo.terms2014-03-03en_ZA
dc.format.extent38 p. : ill.
dc.identifier.citationRobertson, S., Hapgood, J. P. & Louw, A. 2013. Glucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distribution. Steriods, 78(2):182–194, doi.org/10.1016/j.steroids.2012.10.016.en_ZA
dc.identifier.issn0039-128X
dc.identifier.otherdoi.org/10.1016/j.steroids.2012.10.016
dc.identifier.urihttp://hdl.handle.net/10019.1/80932
dc.language.isoen_ZAen_ZA
dc.publisherElsevieren_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectGlucocorticoid receptor levelsen_ZA
dc.subjectDimerizationen_ZA
dc.subjectReceptorsen_ZA
dc.subjectNuclear export rateen_ZA
dc.subjectNuclear focien_ZA
dc.subjectNuclear import rateen_ZA
dc.titleGlucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distributionen_ZA
dc.typeArticleen_ZA
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