title: ORF50-dependent and ORF50-independent activation of the ORF45 gene of Kaposi's sarcoma-associated herpesvirus.
abstract: The ORF45 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a multifunctional tegument protein. Here, we characterize the transcriptional control of the ORF45 gene and show that its promoter can be activated by ORF50 protein, a latent-lytic switch transactivator. The ORF45 promoter can also be induced by sodium butyrate (SB), a histone deacetylase inhibitor, in the absence of ORF50 protein. Although SB induces the ORF45 gene independently of ORF50, its full activation may require the presence of ORF50. Deletion and point mutation analyses revealed that two RBP-Jκ-binding sites in the ORF45 promoter confer the ORF50 responsiveness, whereas NF-Y and Sp1-binding sites mediate the response to SB. Direct binding of NF-Y, Sp1, or RBP-Jκ protein to the ORF45 promoter is required for the promoter activation induced by SB or by ORF50. In conclusion, our study demonstrates both ORF50-dependent and ORF50-independent transcriptional mechanisms operated on the activation of the ORF45 gene.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Pey-Jium
authors.initials: PJ
authors.lastname: Chang
authors.forename: Shie-Shan
authors.initials: SS
authors.lastname: Wang
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Chen
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Hung
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Huang
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Shih
authors.forename: Ju-Bei
authors.initials: JB
authors.lastname: Yen
authors.forename: Jieh-Yuan
authors.initials: JY
authors.lastname: Liou
authors.forename: Lee-Wen
authors.initials: LW
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology; D023081:CCAAT-Binding Factor; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation
chemical_list: D002087:Butyrates; D023081:CCAAT-Binding Factor; D017874:Immediate-Early Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C456286:ORF45 protein, Kaposi's sarcoma-associated herpesvirus; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins; D011494:Protein Kinases; C065999:Sp1 kinase