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 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.
Ikeda
Osamu
O
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University.
Togi
Sumihito
S
Kamitani
Shinya
S
Muromoto
Ryuta
R
Sekine
Yuichi
Y
Nanbo
Asuka
A
Fujimuro
Masahiro
M
Matsuda
Tadashi
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000096:biosynthesis; D008156:Luciferases / Q000235:genetics; D056985:Nuclear Receptor Co-Repressor 2; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D015850:Interleukin-6; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014764:Viral Proteins; D008156:Luciferases