RanBPM regulates Zta-mediated transcriptional activity in Epstein–Barr virus
| Autor: | Shih-Tung Liu, Tse-Yao Chen, Chen-Chia Hung, Ya-Chun Yang, Tzu-Hui Feng, Hsiang-Hung Huang, Li-Kwan Chang |
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| Rok vydání: | 2015 |
| Předmět: |
Gene Expression Regulation
Viral Epstein-Barr Virus Infections Herpesvirus 4 Human Transcription Genetic viruses Mutant SUMO protein Biology medicine.disease_cause Immediate-Early Proteins Small hairpin RNA Virology medicine Humans Gene silencing Gene Transcription factor Adaptor Proteins Signal Transducing Nuclear Proteins biochemical phenomena metabolism and nutrition Epstein–Barr virus Molecular biology Cytoskeletal Proteins Lytic cycle Trans-Activators Protein Binding |
| Zdroj: | Journal of General Virology. 96:2336-2348 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/vir.0.000157 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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