Abstract
Control of cell proliferation and differentiation by the retinoblastoma protein (pRb) depends on its interactions with key cellular substrates. Available data indicate that pRb and the transcription factor Pax 8 play a crucial role in the differentiation of thyroid follicular cells. In this study, we show that pRb takes part in the complex assembled on the thyroperoxidase gene promoter acting as a transcriptional coactivator of Pax 8. Accordingly, pRb interacts with and potentiates Pax 8 transcriptional activity. In addition, we show that the downregulation of pRb gene expression, in thyrocytes, through RNA interference results in a reduction of the thyroperoxidase gene promoter activity mediated by the Pax 8-binding site. In agreement with these results and with the ability of the adenoviral protein E1A to bind pRb, we show that E1A downregulates Pax 8 activity and that such inhibition requires the E1A-Rb interaction. Furthermore, we show that the Pax 8/pRb synergy plays a role on the sodium/iodide symporter gene expression as well.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenovirus E1A Proteins / metabolism
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Binding Sites
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Cells, Cultured
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Chromatin Immunoprecipitation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation*
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Humans
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Iodide Peroxidase / 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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Promoter Regions, Genetic*
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Protein Binding
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Protein Interaction Mapping
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RNA Interference
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Retinoblastoma Protein / antagonists & inhibitors
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism*
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Symporters / metabolism
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Thyroid Gland / cytology
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Thyroid Gland / metabolism
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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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Transcriptional Activation
Substances
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Adenovirus E1A Proteins
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DNA-Binding Proteins
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Nuclear Proteins
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PAX8 Transcription Factor
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PAX8 protein, human
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Paired Box Transcription Factors
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Recombinant Fusion Proteins
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Retinoblastoma Protein
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Symporters
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Trans-Activators
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sodium-iodide symporter
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Iodide Peroxidase
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Glutathione Transferase