Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor Regulates Enhanced Activation of Signal Transducer and Activator of Transcription 3 by Epstein–Barr Virus-Derived Epstein–Barr Nuclear Antigen 2
The Epstein–Barr virus (EBV)-encoded latency protein Epstein–Barr nuclear antigen 2 (EBNA2) is a nuclear transcriptional activator that is essential for EBV-induced cellular transformation. In a previous study, we demonstrated that EBNA2 interacts with signal transducer and activator of transcriptio...
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Veröffentlicht in: | Biological & Pharmaceutical Bulletin 2009/07/01, Vol.32(7), pp.1283-1285 |
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creator | Ikeda, Osamu Togi, Sumihito Kamitani, Shinya Muromoto, Ryuta Sekine, Yuichi Nanbo, Asuka Fujimuro, Masahiro Matsuda, Tadashi |
description | The Epstein–Barr virus (EBV)-encoded latency protein Epstein–Barr nuclear antigen 2 (EBNA2) is a nuclear transcriptional activator that is essential for EBV-induced cellular transformation. In a previous study, we demonstrated that EBNA2 interacts with signal transducer and activator of transcription 3 (STAT3), a signal transducer for an interleukin (IL)-6 family cytokine, and enhances its transcriptional activity. Here, we show that overexpression of a corepressor, silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), decreases the EBNA2-mediated enhanced STAT3 activation. Furthermore, small-interfering RNA-mediated reduction of endogenous SMRT expression augments the EBNA2-mediated enhanced STAT3 activation. Importantly, EBNA2 reduces interactions between STAT3 and SMRT. These data demonstrate that EBNA2 acts as a transcriptional coactivator of STAT3 by influencing the SMRT corepressor complex. |
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In a previous study, we demonstrated that EBNA2 interacts with signal transducer and activator of transcription 3 (STAT3), a signal transducer for an interleukin (IL)-6 family cytokine, and enhances its transcriptional activity. Here, we show that overexpression of a corepressor, silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), decreases the EBNA2-mediated enhanced STAT3 activation. Furthermore, small-interfering RNA-mediated reduction of endogenous SMRT expression augments the EBNA2-mediated enhanced STAT3 activation. Importantly, EBNA2 reduces interactions between STAT3 and SMRT. 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In a previous study, we demonstrated that EBNA2 interacts with signal transducer and activator of transcription 3 (STAT3), a signal transducer for an interleukin (IL)-6 family cytokine, and enhances its transcriptional activity. Here, we show that overexpression of a corepressor, silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), decreases the EBNA2-mediated enhanced STAT3 activation. Furthermore, small-interfering RNA-mediated reduction of endogenous SMRT expression augments the EBNA2-mediated enhanced STAT3 activation. Importantly, EBNA2 reduces interactions between STAT3 and SMRT. These data demonstrate that EBNA2 acts as a transcriptional coactivator of STAT3 by influencing the SMRT corepressor complex.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>19571399</pmid><doi>10.1248/bpb.32.1283</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies, Monoclonal - pharmacology DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - metabolism Epstein-Barr virus Epstein-Barr Virus Nuclear Antigens - metabolism Epstein–Barr nuclear antigen 2 HeLa Cells Humans Immunoblotting Immunoprecipitation Interleukin-6 - biosynthesis Luciferases - genetics Nuclear Receptor Co-Repressor 2 Repressor Proteins - biosynthesis Repressor Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering - genetics SMRT STAT3 STAT3 Transcription Factor - biosynthesis STAT3 Transcription Factor - genetics Transcriptional Activation Transfection Viral Proteins - metabolism |
title | Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor Regulates Enhanced Activation of Signal Transducer and Activator of Transcription 3 by Epstein–Barr Virus-Derived Epstein–Barr Nuclear Antigen 2 |
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