title: Differential effects of Sp cellular transcription factors on viral promoter activation by varicella-zoster virus (VZV) IE62 protein.
abstract: The immediate early (IE) 62 protein is the major varicella-zoster virus (VZV) regulatory factor. Analysis of the VZV genome revealed 40 predicted GC-rich boxes within 36 promoters. We examined effects of ectopic expression of Sp1-Sp4 on IE62- mediated transactivation of three viral promoters. Ectopic expression of Sp3 and Sp4 enhanced IE62 activation of ORF3 and gI promoters while Sp3 reduced IE62 activation of ORF28/29 promoter and VZV DNA replication. Sp2 reduced IE62 transactivation of gI while Sp1 had no significant influence on IE62 activation with any of these viral promoters. Electrophoretic mobility shift assays (EMSA) confirmed binding of Sp1 and Sp3 but not Sp2 and Sp4 to the gI promoter. Sp1-4 bound to IE62 and amino acids 238-258 of IE62 were important for the interaction with Sp3 and Sp4 as well as Sp1. This work shows that Sp family members have differential effects on IE62-mediated transactivation in a promoter-dependent manner.
authors.affiliation: Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, United States; Department of Molecular Biology, National Research Center EL-Buhouth St., Dokki, Cairo, Egypt. Electronic address: mkhalil2@stanford.edu.
authors.forename: Mohamed I
authors.initials: MI
authors.lastname: Khalil
authors.affiliation: Department of Microbiology and Immunology and the Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, NY, United States.
authors.forename: William T
authors.initials: WT
authors.lastname: Ruyechan
authors.affiliation: Department of Microbiology and Immunology and the Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, NY, United States.
authors.forename: John
authors.initials: J
authors.lastname: Hay
authors.affiliation: Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Ann
authors.initials: A
authors.lastname: Arvin
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051704:Sp2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051706:Sp4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; C497119:SP2 protein, human; C497121:SP3 protein, human; C497124:SP4 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D051706:Sp4 Transcription Factor; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D051704:Sp2 Transcription Factor; D051705:Sp3 Transcription Factor
keywords: IE62; Promoters; Sp1; Sp2; Sp3; Sp4; Transcription; VZV