title: RanBPM regulates Zta-mediated transcriptional activity in Epstein-Barr virus.
abstract: Epstein-Barr virus (EBV) expresses two immediate-early proteins, Rta and Zta, which are key transcription factors that can form a complex with MCAF1 at Zta-responsive elements (ZREs) to synergistically activate several viral lytic genes. Our previous research indicated that RanBPM interacts with Rta and enhances Rta sumoylation. Here we showed that RanBPM binds to Zta in vitro and in vivo, and acts as an intermediary protein in Rta-Zta complex formation. The Rta-RanBPM-Zta complex was observed to bind with ZREs in the transcriptional activation of key viral genes, such as BHLF1 and BHRF1, while the introduction of RanBPM short hairpin RNA (shRNA) subsequently reduced the synergistic activity of Zta and Rta. RanBPM was found to enhance Zta-dependent transcriptional activity via the inhibition of Zta sumoylation. Interestingly, Z-K12R, a sumoylation-defective mutant of Zta, demonstrated transcriptional activation capabilities that were stronger than those of Zta and apparently unaffected by RanBPM modulation. Finally, RanBPM silencing inhibited the expression of lytic proteins. Taken together, these results shed light on the mechanisms by which RanBPM regulates Zta-mediated transcriptional activation, and point to an important role for RanBPM in EBV lytic progression.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan, ROC.
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan, ROC.
authors.forename: Tzu-Hui
authors.initials: TH
authors.lastname: Feng
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan, ROC.
authors.forename: Tse-Yao
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan, ROC.
authors.forename: Hsiang-Hung
authors.initials: HH
authors.lastname: Huang
authors.affiliation: Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, Taoyuan, 333, Taiwan, ROC.
authors.forename: Chen-Chia
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, Taoyuan, 333, Taiwan, ROC.
authors.forename: Shih-Tung
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan, ROC.
authors.forename: Li-Kwan
authors.initials: LK
authors.lastname: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D003598:Cytoskeletal Proteins; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D015534:Trans-Activators