Molecular and Cellular Endocrinology
The thyroid hormone receptor a1 (TRa1) is a nuclear receptor for thyroid hormone that shuttles rapidly between the nucleus and cytoplasm. Our prior studies showed that nuclear import of TRa1 is directed by two nuclear localization signals, one in the N-terminal A/B domain and the other in the hinge domain. Here, we showed using in vitro nuclear import assays that TRa1 nuclear localization is temperature and energy-dependent and can be reconstituted by the addition of cytosol. In HeLa cells expressing green fluorescent protein (GFP)-tagged TRa1, knockdown of importin 7, importin B1 and importin a1 by RNA interference, or treatment with an importin B1-specific inhibitor, significantly reduced nuclear localization of TRa1, while knockdown of other importins had no effect. Coimmunoprecipitation assays confirmed that TRa1 interacts with importin 7, as well as importin B1 and the adapter importin B1, suggesting that TRa1 trafficking into the nucleus is mediated by two distinct pathways.
Roggero, Vincent R.; Zhang, Jibo; Parente, Laura E.; Doshi, Yazdi; and Allison, Lizabeth A., Nuclear Import of the Thyroid Hormone Receptor α1 is Mediated by Importin 7, Importin β1, and Adaptor Importin α1 (2016). Molecular and Cellular Endocrinology, 419(C), 185-197.