2013-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656774摘要:EB病毒在溶裂循環的極早期會表現出Rta與Zta兩個轉錄因子,以協同合作的方式活化EB病毒溶裂發展所需的基因。本實驗室先前的研究發現,RanBPM參與Rta與Zta的協同作用,且RanBPM的SUMO修飾在Rta與Zta同時存在下會明顯地降低。在細胞中亦發現Rta能受到泛素化修飾,且Rta與Zta均能與去泛素酵素USP11結合。實驗結果顯示RanBPM能影響EB病毒溶裂循環基因的表現。根據以上初步成果,本研究計畫將近一步探討:(a) SUMO修飾如何影響Rta與Zta的協同作用。(b) USP11是否在Zta-RanBPM-Rta(ZBR)複合體中扮演重要的角色。(c) RanBPM與MCAF1在ZRE序列上的相互作用是否會影響Rta與Zta的協同活化作用。本計畫的研究成果將對於Rta與Zta如何協同地活化溶裂基因以利EB病毒溶裂循環的進行提供更進一步的觀點。<br> Abstract: Epstein-Barr virus (EBV) encodes two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle to activate synergistically the transcription of the genes required for viral lytic development. My current study finds that RanBPM is involved in the Rta-Zta synergy, the interaction between Rta and Zta markedly reduces RanBPM sumoylation, Rta is ubiquitinated in vivo, and USP11, a deubiquitinase, interacts with Rta and Zta. These findings suggest that RanBPM critically influences the expression of EBV lytic genes. Based on these findings, this study will investigate (a) how sumoylation influences the Rta-Zta synergy; (b) if USP11 is important to the formation of the Zta-RanBPM-Rta (ZBR) complex; and (c) whether RanBPM and MCAF1 crosstalk on ZRE to influence synergy. Results from this study will provide further insight into the understanding of the mechanism how Rta and Zta synergistically activate its lytic genes, thus favoring lytic progression.RanBPM蛋白質Zta蛋白質Rta蛋白質EB病毒協同作用RanBPMZtaRtaEBVsynergy深耕型研究計畫【RanBPM 與EB 病毒Rta 及Zta 的協同轉錄】