| Summary: | 碩士 === 國立臺灣大學 === 生化科技學系 === 105 === Epstein-Barr virus is a double stranded DNA oncovirus. The life cycle of EBV can be separated into latent and lytic cycles. The immediate-early proteins, Rta and Zta are necessary for EBV lytic cycle development. They both are viral transactivators that can synergistically activate viral early genes through RanBPM to facilitate viral DNA replication. Our previous study demonstrates that Rta was ubiquitinated by RNF4, a SUMO-targeted ubiquitin E3 ligase, thereby inhibiting lytic progression. Moreover, USP11, a deubiquitinase, has been shown to counteract the functions of RNF4. Our results also suggest that USP11 participates in the reduction of Rta’s ubiquitination by Zta. Firstly, this study showed that Zta utilized USP11 to reduce the amounts of ubiquitinated Rta, but not through the competition of ubiquitins by using ZK12R, a Zta sumoylation-defective mutant. This study further demonstrated by using a catalytic mutant of USP11 that USP11 is a deubiquitinase of Rta. Moreover, the experiments of gene knockdown confirmed that the ubiquitination of Rta is affected by USP11 and RanBPM. However, Zta’s ubiquitination depends on USP11. Meanwhile, the deubiquitination of Rta by USP11 requires the participation of RanBPM since downregulation of RanBPM inhibites USP11-mediated deubiquitination of Rta. Although RanBPM is necessary in the USP11-mediated Rta deubiquitination, this study found that Zta is able to decrease Rta’s ubiquitination when RanBPM is knocked down by shRNA. This study also showed that EBV lytic cycle was repressed in P3HR1 cells with USP11 silencing. Altogether, this study reveals that Zta is involved in the USP11-mediated deubiquitination of Rta to stabilize Rta to promote EBV lytic development.
|
|---|
