Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors.
Confocal microscopy and cell fractionation studies have revealed the residence of nuclear thyroid hormone receptors (TR) in cytoplasm. Treatment of cells with the hormone (L-thyroxine or 3,5,3'-triiodo-L-thyronine, T(3)) results in shuttling of TR into the nuclear compartment. Confocal microscopy has also disclosed that TR in the nuclear compartment is redistributed in response to exposure of cells to iodothyronine. The TRbeta1 isoform may be found in cytoplasm of thyroid hormone-treated cells complexed with other proteins, such as mitogen-activated protein kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and nuclear receptor coactivators. Formation of such complexes may facilitate nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell proliferation (MAPK). Nuclear retention of TRalpha1 is also increased by T(3). It is not clear that iodothyronines have primary effects on nuclear export of TRs. Thyroid hormone may also increase cytoplasm-to-nucleus partitioning of p53 and certain signal-transducing pathway proteins. A monomer derived from the cell surface receptor for thyroid hormone on integrin alphavbeta3 that does not share homologies with TR may move to the cell nucleus in thyroid hormone-treated cells. Because cells in the intact organism are tonically exposed to thyroid hormone, the latter is likely to contribute to the basal rate of nuclear import of thyroid hormone receptors.
Davis
Paul J
PJ
Ordway Research Institute, Inc., Albany Medical College and Stratton VA Medical Center, 150 New Scotland Avenue, Albany, NY 12208, USA. pdavis@ordwayresearch.org
Davis
Faith B
FB
Lin
Hung-Yun
HY
D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D003599:Cytoskeleton; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D018613:Microscopy, Confocal; D008954:Models, Biological; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions; D013963:Thyroid Hormones / Q000378:metabolism*
D000199:Actins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones