RanBPM regulates Zta-mediated transcriptional activity in Epstein-Barr virus

Ya Chun Yang, Tzu Hui Feng, Tse Yao Chen, Hsiang Hung Huang, Chen Chia Hung, Shih Tung Liu, Li Kwan Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

10 Scopus citations


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.

Original languageEnglish
Pages (from-to)2336-2348
Number of pages13
JournalJournal of General Virology
Issue number8
StatePublished - 01 08 2015

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© 2015 The Authors.


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