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Human testicular orphan receptor 4 enhances thyroid hormone receptor signaling
Author(s) -
Huang YaHui,
Liao ChenHsin,
Chen RueyNan,
Liao ChiaJung,
Lin KwangHuei
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21959
Subject(s) - thyroid hormone receptor , orphan receptor , nuclear receptor , receptor , neuron derived orphan receptor 1 , thyroid hormone receptor beta , transcription factor , biology , cell growth , signal transduction , chromatin immunoprecipitation , microbiology and biotechnology , transcription (linguistics) , hormone receptor , gene , gene expression , promoter , biochemistry , genetics , linguistics , philosophy , breast cancer , cancer
Abstract The thyroid hormone receptor (TR) and human testicular orphan receptor 4 (TR4) belong to the nuclear hormone receptor superfamily. They are ligand‐dependent transcription factors. TR and TR4 bind to a similar thyroid response element (TRE), known as a direct repeat with four nucleotide spacing (DR4). This study examined the possible interaction or cross‐talking between those two receptors. We hypothesized that protein–protein interaction between TR4 and TR may promote TR‐mediated transcriptional activity. Glutathione S ‐transferase pull‐down and immunoprecipitation assays showed direct interaction between TR and TR4. Electrophoretic mobility‐shift assay demonstrated that TR and TR4 could co‐occupy the same TRE. The interaction between TR4 and TR may enhance regulation of genes targeted by TR, such as furin, fibrinogen, cdk2 and p21 expression. We found that TR4 function is similar with TR as TR4 alone could regulate expression of some TR target genes, and could increase cell migration or inhibit cell proliferation. Importantly, the TR‐dependent inhibition of cell proliferation and stimulation of cell migration are more enhanced in the HepG2‐TR cells stably over‐expressing TR4. Overall, TR4 not only has modulation abilities similar to TR but also can cross‐talk with TR and promote the TR signaling pathway. J. Cell. Physiol. 222: 347–356, 2010. © 2009 Wiley‐Liss, Inc.