2013-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/680100摘要：EB病毒在溶裂期生活史的極早期會表現出Rta與Zta兩個轉錄因子，以協同合作的方式活化EB病毒溶裂期發展所需的基因。本實驗室先前的研究發現，RNF4能將受到SUMO-2修飾的Rta蛋白質進行泛素化修飾，因而抑制EB病毒溶裂期的發展。RNF4亦能與Zta結合並在細胞體外的環境中促進Zta的泛素化修飾。另外，Zta能抑制Rta的泛素化修飾，由於其與Rta均能結合於RNF4蛋白質的N端，表示Zta可能透過干擾RNF4與Rta的結合而影響Rta的泛素化修飾。根據以上實驗結果，本研究將探討 (a) RNF4是否為Zta的STUbL而將其進行泛素化修飾，以及 (b) Zta如何拮抗RNF4的功能而影響其對Rta泛素化修飾的調控。本研究結果將對Rta及Zta如何與宿主蛋白質進行交互作用，並能協同地促進溶裂期發展提供更進一步的了解。<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. Our recent study indicates that RNF4 targets SUMO-2-modified Rta for ubiquitination, thus inhibiting EBV lytic cycle. RNF4 also interacts with Zta and promotes its ubiquitination in vitro. In addition, Zta decreases the ubiquitination of Rta, and both Rta and Zta bind to the N-terminal of RNF4, indicating that Zta may interfere the interaction between RNF4 and Rta by binding to RNF4. Based on these findings, this study will investigate (a) whether RNF4 acts as an STUbL for targeting Zta for ubiquitination; and (b) how Zta antagonizes the function of RNF4 to influence the ubiquitination of Rta. Results from this study will provide further insight into the understanding of the mechanism how Rta and Zta interplay with a host protein, thus synergistically promote lytic progression.