Multiple exportins influence thyroid hormone receptor localization

作者：Subramanian Kelly S; Dziedzic Rose C; Nelson Hallie N; Stern Mary E; Roggero Vincent R; Bondzi Cornelius; Allison Lizabeth A^*

来源：Molecular and Cellular Endocrinology, 2015, 411(C): 86-96.

DOI：10.1016/j.mce.2015.04.014

• Thyroid hormone receptor
• Thyroid hormone
• Nuclear export
• Exportin

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/calreticulin-mediated 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 toward 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.

• 出版日期2015-8-15