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

Abstract

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. © 2009 Pharmaceutical Society of Japan.