title: Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3.
abstract: The alphaherpesvirus serine/threonine kinase Us3 plays diverse roles in virus multiplication and modifies both nuclear and cytoplasmic substrates. We recently reported that treatment of HSV-2 Us3-transfected and HSV-2-infected cells with leptomycin B, an inhibitor of nuclear export mediated by interaction of chromosomal regional maintenance protein (CRM1) with leucine rich nuclear export signals (NESs), resulted in nuclear trapping of Us3. Here, we utilized fluorescence loss in photobleaching to monitor nuclear export of HSV-2 Us3 and confirm that this process proceeds solely via a CRM1-mediated mechanism. Analysis of deletion derivatives of HSV-2 Us3 fused to a nuclear export reporter protein implicated the involvement of NES-like sequences in nuclear export. However, nuclear trapping of HSV-2 Us3 proteins carrying mutations in these potential NESs was not observed, indicating that these sequences are not functional in the context of full-length protein. Our analyses also revealed previously unidentified regions of HSV-2 Us3 that contribute to its kinase activity.
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors: Renée L
authors: RL
authors: Finnen
authors: Susan M
authors: SM
authors: Johnston
authors: Casey E
authors: CE
authors: Neron
authors: Bruce W
authors: BW
authors: Banfield
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D057809:HEK293 Cells; D018258:Herpesvirus 2, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C084395:US3 protein, Human herpesvirus 2