https://scholars.lib.ntu.edu.tw/handle/123456789/414773
標題: | Role of RNF4 in the Ubiquitination of Rta of Epstein-Barr Virus | 作者: | Y. C. Yang Y. Yoshikai S. W. Hsu H. Saitoh L. K. Chang |
公開日期: | 2013 | 出版社: | American Society for Biochemistry and Molecular Biology | 卷: | 288 | 期: | 18 | 起(迄)頁: | 12866-12879 | 來源出版物: | Journal of Biological Chemistry | 摘要: | Epstein-Barr virus (EBV) encodes a transcription factor, Rta, which is required to activate the transcription of EBV lytic genes. This study demonstrates that treating P3HR1 cells with a proteasome inhibitor, MG132, causes the accumulation of SUMO-Rta and promotes the expression of EA-D. GST pull-down and coimmunoprecipitation studies reveal that RNF4, a RING-domain-containing ubiquitin E3 ligase, interacts with Rta. RNF4 also targets SUMO-2-conjugated Rta and promotes its ubiquitination in vitro. Additionally, SUMO interaction motifs in RNF4 are important to the ubiquitination of Rta because the RNF4 mutant with a mutation at the motifs eliminates ubiquitination. The mutation of four lysine residues on Rta that abrogated SUMO-3 conjugation to Rta also decreases the enhancement of the ubiquitination of Rta by RNF4. This finding demonstrates that RNF4 is a SUMO-targeted ubiquitin E3 ligase of Rta. Finally, knockdown of RNF4 enhances the expression of Rta and EA-D, subsequently promoting EBV lytic replication and virions production. Results of this study significantly contribute to efforts to elucidate a SUMO-targeted ubiquitin E3 ligase that regulates Rta ubiquitination to influence the lytic development of EBV |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/414773 | ISSN: | 1083351X | DOI: | 10.1074/jbc.M112.413393 |
顯示於: | 生化科技學系 |
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