title: Epstein-Barr virus transcription activator Rta upregulates decoy receptor 3 expression by binding to its promoter.
abstract: Decoy receptor 3 (DcR3) is a soluble decoy receptor belonging to the tumor necrosis factor receptor superfamily that is overexpressed in various malignant tumor types. DcR3 has been implicated in tumor cell survival by inhibiting apoptosis and by interfering with immune surveillance. A previous study showed that DcR3 expression is associated with Epstein-Barr virus (EBV)-positive lymphomas but rarely with non-EBV-positive B-cell lymphomas, suggesting that the presence of EBV may affect DcR3 expression. Here, we demonstrated enhanced DcR3 expression upon EBV reactivation in P3HR1 cells and in EBV-infected 293 cells. This enhancement, however, could not be detected in 293 cells infected with EBV with BRLF1 deleted. We found that EBV transactivator, Rta, could upregulate DcR3 expression by direct binding to an Rta-responsive element (RRE) located in the DcR3 promoter region and that this RRE is important for Rta-mediated DcR3 expression. Overexpressing CREB-binding protein (CBP) further enhanced Rta-dependent DcR3 expression, suggesting Rta-dependent DcR3 transcription activity is mediated by CBP. Previously, Rta was shown to enhance phosphatidylinositol-3 kinase (PI3-K) activity. However, Rta-transduced PI 3-K activity plays a minor role in DcR3 expression. This is the first report to demonstrate that Rta upregulates a cellular gene by direct binding to an RRE.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Number 155 Section 2 Linong Street, Taipei 112, Taiwan.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Ho
authors.forename: Chen-Fang
authors.initials: CF
authors.lastname: Hsu
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Fong
authors.forename: Shyh-Kuan
authors.initials: SK
authors.lastname: Tai
authors.forename: Shie-Liang
authors.initials: SL
authors.lastname: Hsieh
authors.forename: Chi-Ju
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008156:Luciferases; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C068382:BRLF1 protein, Human herpesvirus 4; D017931:DNA Primers; D017874:Immediate-Early Proteins; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D015534:Trans-Activators; D014764:Viral Proteins; D008156:Luciferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human