scholarly journals Differential Expression of Thyroid Hormone Receptor Isoforms Dictates the Dominant Negative Activity of Mutant β Receptor

2002 ◽  
Vol 16 (9) ◽  
pp. 2077-2092 ◽  
Author(s):  
Xiao-Yong Zhang ◽  
Masahiro Kaneshige ◽  
Yuji Kamiya ◽  
Kumiko Kaneshige ◽  
Peter McPhie ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Differential Expression ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Dominant Negative ◽  
Receptor Isoforms ◽  
Β Receptor ◽  
Dominant Negative Activity

scholarly journals Thyroid-hormone-dependent negative regulation of thyrotropin beta gene by thyroid hormone receptors: study with a new experimental system using CV1 cells

2004 ◽  
Vol 378 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Keiko NAKANO ◽  
Akio MATSUSHITA ◽  
Shigekazu SASAKI ◽  
Hiroko MISAWA ◽  
Kozo NISHIYAMA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Experimental System ◽  
Thyroid Stimulating Hormone ◽  
Negative Regulation ◽  
Dominant Negative ◽  
Negative Effects ◽  
Receptor Isoforms

The molecular mechanism involved in the liganded thyroid hormone receptor suppression of the TSHβ (thyroid-stimulating hormone β, or thyrotropin β) gene transcription is undetermined. One of the main reasons is the limitation of useful cell lines for the experiments. We have developed an assay system using non-pituitary CV1 cells and studied the negative regulation of the TSHβ gene. In CV1 cells, the TSHβ–CAT (chloramphenicol acetyltransferase) reporter was stimulated by Pit1 and GATA2 and suppressed by T3 (3,3´,5-tri-iodothyronine)-bound thyroid hormone receptor. The suppression was dependent on the amounts of T3 and the receptor. Unliganded receptor did not stimulate TSHβ activity, suggesting that the receptor itself is not an activator. Analyses using various receptor mutants revealed that the intact DNA-binding domain is crucial to the TSHβ gene suppression. Co-activators and co-repressors are not necessarily essential, but are required for the full suppression of the TSHβ gene. Among the three receptor isoforms, β2 exhibited the strongest inhibition and its protein level was the most predominant in a thyrotroph cell line, TαT1, in Western blotting. The dominant-negative effects of various receptor mutants measured on the TSHβ–CAT reporter were not simple mirror images of those in the positive regulation under physiological T3 concentration.

scholarly journals Oncogenic conversion of the thyroid hormone receptor by altered nuclear transport

2006 ◽  
Vol 4 (1) ◽  
pp. nrs.04008 ◽  
Author(s):  
Ghislain M.C. Bonamy ◽  
Lizabeth A. Allison
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathways ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Direct Interaction ◽  
Dominant Negative ◽  
Multiple Cell ◽  
Dominant Negative Activity ◽  
Dominant Negative Variant ◽  
Complex Signaling

Nuclear receptors (NRs) are transcription factors whose activity is modulated by ligand binding. These receptors are at the core of complex signaling pathways and act as integrators of many cellular signals. In the last decade our understanding of NRs has greatly evolved. In particular, regulation of NR subcellular dynamics has emerged as central to their activity. Research on the subcellular distribution of the thyroid hormone receptor (TR) has revealed new dimensions in the complexity of NR regulation, and points to the possibility that NR mislocalization plays a key role in oncogenesis. For many years, TR was thought to reside exclusively in the nucleus. It is now known that TR is a dynamic protein that shuttles between the nucleus and cytoplasm. TR is localized to the nucleus in a phosphorylated form, suggesting that compartment-specific phosphorylation mediates cross-talk between multiple cell signaling pathways. The oncoprotein v-ErbA, a viral-derived dominant negative variant of TR is actively exported to the cytoplasm by the CRM1 export receptor. Strikingly, the oncoprotein causes mislocalization of cellular TR and some of its coactivators by direct interaction. Here, we offer some perspectives on the role of subcellular trafficking in the oncogenic conversion of TR, and propose a new model for oncoprotein dominant negative activity.

Differential expression of thyroid hormone receptor isoforms in neurons and astroglial cells.

Endocrinology ◽  
1994 ◽  
Vol 135 (2) ◽  
pp. 548-555 ◽  
Author(s):  
J L Leonard ◽  
A P Farwell ◽  
P M Yen ◽  
W W Chin ◽  
M Stula
Keyword(s):  
Thyroid Hormone ◽  
Differential Expression ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Astroglial Cells ◽  
Receptor Isoforms
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