Activation of AP-1-mediated transcription by Rta of Epstein-Barr virus

• Main Authors: Hong-Mine Yeh, 葉弘銘
• Other Authors: Yi-Ren Hong
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/47043511224756465467

碩士 === 高雄醫學大學 === 醫學遺傳學研究所碩士班 === 94 === Epstein-Barr virus (EBV) has two life cycles. The virus is normally maintained in infected host cell under latent conditions but enters a lytic cycle to proliferate after exposing to specific chemical or physical stimuli. Expression of Rta and Zta by EBV is the key event leading to the lytic activation. Rta is a transcription factor encoded by BRLF1 of EBV, which is expressed during the immediate-early stage of the lytic cycle to activate the genes required for EBV lytic development. Meanwhile, MBD1-containing chromatin-associated factor (MCAF1) interacts with MBD1 and Sp1; this interaction is crucial to MBD1-mediated transcriptional repression. Howerever, when MCAF1 binds to Sp1, MCAF1 becomes a coactivator to enhance Sp1-mediated transcription. AP-1 are transcription factors involving in cellular proliferation, differentiation and apoptosis. In this study, transcription of BZLF1 transactivated by Rta was examined by transient reporter assay, which shows that Rta activates the transcription of BZLF1 through the binding at the ZII domain. Moreover, the study reveals the binding Rta, MCAF1 and AP-1 (ATF2, c-Jun, c-Fos and ATF1) to the ZII domain in the BZLF1 promoter and forms a AP-1-MCAF1-Rta complex. Addtionally, this study aslo shows that the N-terminal 323 amino acids in ATF2 interacts with the region in MCAF1 between amino acids 562 and 650. This study demonstrates that MCAF1 is the mediator between Rta and AP-1, which facilitates an indirect interaction between Rta and AP-1 on the ZII region in the BZLF1 promoter and activates AP-1-mediated transcription. Our study documents the critical role of Rta in regulating AP-1-mediated transcription.