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Multiple Exportins Influence Thyroid Hormone Receptor Localization
Subramanian, Kelly Dziedzic, Rose C. Nelson, Hallie N. Stern, Mary E. Roggero, Vincent R. Bondzi, Cornelius Allison, Lizabeth A.
Subramanian, Kelly
Dziedzic, Rose C.
Nelson, Hallie N.
Stern, Mary E.
Roggero, Vincent R.
Bondzi, Cornelius
Allison, Lizabeth A.
Abstract
The thyroid hormone receptor (TR) undergoes nucleocytoplasmic shuttling and regulates target genes involved in metabolism and development. Previously, we showed that TR follows a CRM1/calreticulinmediated nuclear export pathway. However, two lines of evidence suggest TR also follows another pathway: export is only partially blocked by leptomycin B (LMB), a CRM1-specific inhibitor; and we identified nuclear export signals in TR that are LMB-resistant. To determine whether other exportins are involved in TR shuttling, we used RNA interference and fluorescence recovery after photobleaching shuttling assays in transfected cells. Knockdown of exportins 4, 5, and 7 altered TR shuttling dynamics, and when exportins 5 and 7 were overexpressed, TR distribution shifted towards the cytosol. To further assess the effects of exportin overexpression, we examined transactivation of a TR-responsive reporter gene. Our data indicate that multiple exportins influence TR localization, highlighting a fine balance of nuclear import, retention, and export that modulates TR function.
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2015-08-01
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Biology
DOI
https://doi.org/10.1016/j.mce.2015.04.014