Nuclear import of the thyroid hormone receptor ?1 is mediated by importin 7, importin ?1, and adaptor importin ?1.

ABSTRACT: The thyroid hormone receptor ?1 (TR?1) is a nuclear receptor for thyroid hormone that shuttles rapidly between the nucleus and cytoplasm. Our prior studies showed that nuclear import of TR?1 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 TR?1 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 TR?1, knockdown of importin 7, importin ?1 and importin ?1 by RNA interference, or treatment with an importin ?1-specific inhibitor, significantly reduced nuclear localization of TR?1, while knockdown of other importins had no effect. Coimmunoprecipitation assays confirmed that TR?1 interacts with importin 7, as well as importin ?1 and the adapter importin ?1, suggesting that TR?1 trafficking into the nucleus is mediated by two distinct pathways.

SUBMITTER: Roggero VR 

PROVIDER: S-EPMC4684427 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature