Abstract
TGF-beta1 is a potent inhibitor of growth and DNA synthesis in thyroid cells. It has also been shown that TGF-beta1 inhibits thyrocyte function. The functional inhibition is represented by a downregulation of thyroid specific genes, such as Na(+)/I(-) symporter (NIS), thyroglobulin (TG) and thyroperoxidase (TPO). The transcriptional control of these genes is mediated by thyroid-specific transcription factors: thyroid transcription factor-1 (TTF-1) and PAX-8. It has been shown that Smad proteins play a pivotal role in the intracellular signal transduction of the TGF-beta family members. In this paper, the functional relevance of Smad4, in the control of thyroid differentiation genes and thyroid-specific transcription factors, has been investigated. The data obtained provides, for the first time, evidence that D.N. Smad4-100T is capable of blocking TGF-beta1 action in the regulation of thyroid-specific genes expression. Such action is possible by blocking nuclear translocation of Smad4 and Smad2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens / genetics
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Autoantigens / physiology
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Blotting, Northern
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Blotting, Western
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Cell Differentiation / drug effects*
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Cell Line
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Clone Cells
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Down-Regulation
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Gene Expression Regulation / drug effects
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Genetic Vectors / genetics
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Immunohistochemistry
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Iodide Peroxidase / genetics
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Iodide Peroxidase / physiology
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Iron-Binding Proteins / genetics
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Iron-Binding Proteins / physiology
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Luciferases / genetics
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Luciferases / metabolism
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Mutation / genetics
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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PAX8 Transcription Factor
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Paired Box Transcription Factors
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Phosphorylation
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Rats
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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Smad2 Protein
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Smad4 Protein
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Symporters / genetics
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Symporters / physiology
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Thyroid Gland / cytology
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Thyroid Gland / drug effects*
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Thyroid Nuclear Factor 1
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Thyrotropin / pharmacology
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Trans-Activators / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Transforming Growth Factor beta / pharmacology*
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Transforming Growth Factor beta / physiology
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Transforming Growth Factor beta1
Substances
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Autoantigens
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DNA-Binding Proteins
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Iron-Binding Proteins
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NKX2-1 protein, human
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Nkx2-1 protein, rat
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Nuclear Proteins
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PAX8 Transcription Factor
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Paired Box Transcription Factors
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Pax8 protein, rat
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Recombinant Fusion Proteins
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Smad2 Protein
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Smad2 protein, rat
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Smad4 Protein
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Smad4 protein, rat
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Symporters
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TGFB1 protein, human
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Tgfb1 protein, rat
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Thyroid Nuclear Factor 1
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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sodium-iodide symporter
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Thyrotropin
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TPO protein, human
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Iodide Peroxidase
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Luciferases
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Cysteine Endopeptidases
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cysteine proteinase I