title: The carboxy terminus of the herpesvirus saimiri ORF 57 gene contains domains that are required for transactivation and transrepression.
abstract: Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes of herpesviruses. We have previously shown that ORF 57 encodes a multifunctional protein, responsible for both transactivation and repression of viral gene expression at a post-transcriptional level. This suggests that the ORF 57 protein shares some functional similarities with the herpes simplex virus IE63/ICP27 and Epstein-Barr virus Mta proteins. However, little is known about the functional domains responsible for the properties of ORF 57 due to the limited homology shared between these proteins. In this report, we have identified the functional domains responsible for transactivation and repression by the ORF 57 protein. We demonstrate that the carboxy terminus is required for ORF 57 transactivation, repression and an intense SC-35 nuclear spotting. This region contains two highly conserved motifs amongst its homologues, a zinc finger-like motif and a highly hydrophobic domain. We further show that the hydrophobic domain is required for transactivation and is also involved in nuclear localization of the ORF 57 protein, whereas the zinc finger-like domain is required for transactivation, repression and the intense SC-35 nuclear spotting.
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK1.
authors.forename: Delyth J
authors.initials: DJ
authors.lastname: Goodwin
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK1.
authors.forename: Kersten T
authors.initials: KT
authors.lastname: Hall
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK1.
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Giles
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK1.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Calderwood
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK1.
authors.forename: Alex F
authors.initials: AF
authors.lastname: Markham
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK1.
authors.forename: Adrian
authors.initials: A
authors.lastname: Whitehouse
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016645:Aotidae; D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021281:Quantitative Structure-Activity Relationship; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D014764:Viral Proteins; D016335:Zinc Fingers / Q000235:genetics
chemical_list: C415247:ORF57 protein, Herpesvirus saimiri; D012097:Repressor Proteins; D015534:Trans-Activators; D014764:Viral Proteins