期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 419, 期 C, 页码 185-197出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2015.10.016
关键词
Thyroid hormone receptor; Thyroid hormone; Nuclear import; Importin
资金
- National Institutes of Health [2R15DK058028-03]
- National Science Foundation [MCB 1120513]
- Charles Center at the College of William and Mary
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1120513] Funding Source: National Science Foundation
The thyroid hormone receptor alpha 1 (TR alpha 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 alpha 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 alpha 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 alpha 1, knockdown of importin 7, importin beta 1 and importin alpha 1 by RNA interference, or treatment with an importin beta 1-specific inhibitor, significantly reduced nuclear localization of TR alpha 1, while knockdown of other importins had no effect. Coimmunoprecipitation assays confirmed that TR alpha 1 interacts with importin 7, as well as importin beta 1 and the adapter importin alpha 1, suggesting that TR alpha 1 trafficking into the nucleus is mediated by two distinct pathways. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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