Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-β via Smad4 binding element in human BL cells

Chih Lung Liang, Chi Neu Tsai, Pei-Jung Chung, Jo Lin Chen, Cheng Ming Sun, Ruey Hwa Chen, Ji-Hong Hong, Yu Sun Chang

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations

Abstract

In Epstein-Barr virus (EBV)-infected BL cells, the oncogenic EBV-encoded nuclear antigen 1 (EBNA 1) gene is directed from the latent promoter Qp. Yeast one-hybrid screen analysis using the -50 to -37 sequence of Qp as the bait was carried out to identify transcriptional factors that may control Qp activity. Results showed that Smad4 binds the -50 to -37 sequence of Qp, indicating that this promoter is potentially regulated by TGF-β. The association of Smad4 with Qp was further confirmed by supershift of EMSA complexes using Smad4-specific antibody. The transfection of a Qp reporter construct in two EBV(+) BL cell lines, Rael and WW2, showed that Qp activity is repressed in response to the TGF-β treatment. This repression involves the interaction of a Smad3/Smad4 complex and the transcriptional repressor TGIF, as determined by cotransfection assay and coimmunoprecipitation analysis. Results suggest that TGF-β may transcriptionally repress Qp through the Smad4-binding site in human BL cells. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)184-192
Number of pages9
JournalVirology
Volume277
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • BL cells
  • EBV
  • Qp
  • Smad4
  • TGF-β
  • TGIF

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