Nuclear Export of TRβ

Thyroid hormone receptors (TRs) bind to DNA to control gene transcription involved with metabolism, growth, and development. These nuclear receptors shuttle between the nucleus and cytoplasm but are primarily found in the nucleus. Although TRs have been shown to be able to use a CRM1‐dependent pathway, TRs also utilize CRM1‐independent nuclear export pathways. Both CRM1‐independent and dependent NESs are present in TR. In vivo approaches with HeLa cells transfected with GFP‐TRβ were used to investigate TRβ nuclear export. RNA interference from shRNA was used to knock‐down transportin 1, transportin 2, exportin 5, and exportin 6 gene expression. Treatment with leptomycin B, a specific inhibitor of CRM1, was used to block CRM1‐dependent pathways. Visualization of HeLa cells showed changes in the compartmentalization of TRβ with addition of leptomycin B. When CRM1 export pathway was blocked, TRβ shifted towards a more nuclear distribution. Inhibiting CRM1 and knocking‐down transportin 1, transportin 2, exportin 5, and exportin 6 expression showed no additional change in TRβ distribution. To date, exportins 4 and 7 remain to be tested. Since TRs can use CRM1‐independent pathways, there must be other exportin(s) TRs can use in their nuclear export; however, additional approaches to study rapid nuclear export in real‐time are needed to further characterize the exact mechanism.