1887

Abstract

The UL97 protein kinase is a serine/threonine kinase expressed by human cytomegalovirus (CMV) that phosphorylates ganciclovir. An investigation of the subcellular localization of pUL97 in infected cells indicated that, early in infection, pUL97 localized to focal sites in the nucleus that transitioned to subnuclear compartments and eventually throughout the entire nucleus. When UL97 kinase activity was eliminated with a K355M mutation or pharmacologically inhibited with maribavir, the expansion and redistribution of pUL97 foci within the nucleus was delayed, nuclear reorganization did not occur and assembly complexes in the cytoplasm failed to form normally. As UL97 kinase and its homologues appear to be functionally related to CDK1, a known regulator of nuclear structural organization, the effects of the UL97 kinase on CDK1 were investigated. Expression of CDK1 in infected cells appeared to be induced by UL97 kinase activity at the level of transcription and was not tied to other virus life-cycle events, such as viral DNA replication or virion assembly. These results suggest that, in addition to phosphorylating CDK1 targets, the UL97 kinase modifies G/M cell-cycle checkpoint regulators, specifically CDK1, to promote virus replication.

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2012-08-01
2019-10-20
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References

  1. Anon. . ( 2007; ). Maribavir: 1263W94, Benzimidavir, GW 1263, GW 1263W94, VP41263. . Drugs R D 8:, 188–192.[PubMed] [CrossRef]
    [Google Scholar]
  2. Advani S. J. , Brandimarti R. , Weichselbaum R. R. , Roizman B. . ( 2000; ). The disappearance of cyclins A and B and the increase in activity of the G2/M-phase cellular kinase cdc2 in herpes simplex virus 1-infected cells require expression of the α22/US1.5 and UL13 viral genes. . J Virol 74:, 8–15. [CrossRef] [PubMed]
    [Google Scholar]
  3. Advani S. J. , Weichselbaum R. R. , Roizman B. . ( 2003a; ). Herpes simplex virus 1 activates cdc2 to recruit topoisomerase IIα for post-DNA synthesis expression of late genes. . Proc Natl Acad Sci U S A 100:, 4825–4830. [CrossRef] [PubMed]
    [Google Scholar]
  4. Advani S. J. , Weichselbaum R. R. , Roizman B. . ( 2003b; ). Herpes simplex virus 1 activates cdc2 to recruit topoisomerase IIα for post-DNA synthesis expression of late genes. . Proc Natl Acad Sci U S A 100:, 4825–4830. [CrossRef] [PubMed]
    [Google Scholar]
  5. Arcangeletti M. C. , De Conto F. , Ferraglia F. , Pinardi F. , Gatti R. , Orlandini G. , Calderaro A. , Motta F. , Medici M. C. . & other authors ( 2003; ). Human cytomegalovirus proteins PP65 and IEP72 are targeted to distinct compartments in nuclei and nuclear matrices of infected human embryo fibroblasts. . J Cell Biochem 90:, 1056–1067. [CrossRef] [PubMed]
    [Google Scholar]
  6. Azzeh M. , Honigman A. , Taraboulos A. , Rouvinski A. , Wolf D. G. . ( 2006; ). Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity. . Virology 354:, 69–79. [CrossRef] [PubMed]
    [Google Scholar]
  7. Baek M.-C. , Krosky P. M. , He Z. , Coen D. M. . ( 2002; ). Specific phosphorylation of exogenous protein and peptide substrates by the human cytomegalovirus UL97 protein kinase. Importance of the P+5 position. . J Biol Chem 277:, 29593–29599. [CrossRef] [PubMed]
    [Google Scholar]
  8. Biron K. K. . ( 2006; ). Antiviral drugs for cytomegalovirus diseases. . Antiviral Res 71:, 154–163. [CrossRef] [PubMed]
    [Google Scholar]
  9. Biron K. K. , Harvey R. J. , Chamberlain S. C. , Good S. S. , Smith A. A. III , Davis M. G. , Talarico C. L. , Miller W. H. , Ferris R. . & other authors ( 2002; ). Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole l-riboside with a unique mode of action. . Antimicrob Agents Chemother 46:, 2365–2372. [CrossRef] [PubMed]
    [Google Scholar]
  10. Britt W. . ( 2008; ). Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease. . Curr Top Microbiol Immunol 325:, 417–470. [CrossRef] [PubMed]
    [Google Scholar]
  11. Cano-Monreal G. L. , Tavis J. E. , Morrison L. A. . ( 2008; ). Substrate specificity of the herpes simplex virus type 2 UL13 protein kinase. . Virology 374:, 1–10. [CrossRef] [PubMed]
    [Google Scholar]
  12. Cano-Monreal G. L. , Wylie K. M. , Cao F. , Tavis J. E. , Morrison L. A. . ( 2009; ). Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins. . Virology 392:, 137–147. [CrossRef] [PubMed]
    [Google Scholar]
  13. Caretti G. , Salsi V. , Vecchi C. , Imbriano C. , Mantovani R. . ( 2003; ). Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters. . J Biol Chem 278:, 30435–30440. [CrossRef] [PubMed]
    [Google Scholar]
  14. Chae H.-D. , Yun J. , Bang Y.-J. , Shin D. Y. . ( 2004; ). Cdk2-dependent phosphorylation of the NF-Y transcription factor is essential for the expression of the cell cycle-regulatory genes and cell cycle G1/S and G2/M transitions. . Oncogene 23:, 4084–4088. [CrossRef] [PubMed]
    [Google Scholar]
  15. Chevillotte M. , Landwehr S. , Linta L. , Frascaroli G. , Lüske A. , Buser C. , Mertens T. , von Einem J. . ( 2009; ). Major tegument protein pp65 of human cytomegalovirus is required for the incorporation of pUL69 and pUL97 into the virus particle and for viral growth in macrophages. . J Virol 83:, 2480–2490. [CrossRef] [PubMed]
    [Google Scholar]
  16. Chou S. . ( 2008; ). Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir. . Rev Med Virol 18:, 233–246. [CrossRef] [PubMed]
    [Google Scholar]
  17. Cinatl J. Jr , Scholz M. , Doerr H. W. . ( 2005; ). Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulation. . Med Res Rev 25:, 167–185. [CrossRef] [PubMed]
    [Google Scholar]
  18. Cobbs C. S. , Soroceanu L. , Denham S. , Zhang W. , Kraus M. H. . ( 2008; ). Modulation of oncogenic phenotype in human glioma cells by cytomegalovirus IE1-mediated mitogenicity. . Cancer Res 68:, 724–730. [CrossRef] [PubMed]
    [Google Scholar]
  19. Dittmer D. , Mocarski E. S. . ( 1997; ). Human cytomegalovirus infection inhibits G1/S transition. . J Virol 71:, 1629–1634.[PubMed]
    [Google Scholar]
  20. Finch J. S. , Rosenberger S. F. , Martinez J. D. , Bowden G. T. . ( 2001; ). Okadaic acid induces transcription of junB through a CCAAT box and NF-Y. . Gene 267:, 135–144. [CrossRef] [PubMed]
    [Google Scholar]
  21. Gill R. B. , Frederick S. L. , Hartline C. B. , Chou S. , Prichard M. N. . ( 2009; ). Conserved retinoblastoma protein-binding motif in human cytomegalovirus UL97 kinase minimally impacts viral replication but affects susceptibility to maribavir. . Virol J 6:, 9. [CrossRef] [PubMed]
    [Google Scholar]
  22. Goldberg M. D. , Honigman A. , Weinstein J. , Chou S. , Taraboulos A. , Rouvinski A. , Shinder V. , Wolf D. G. . ( 2011; ). Human cytomegalovirus UL97 kinase and nonkinase functions mediate viral cytoplasmic secondary envelopment. . J Virol 85:, 3375–3384. [CrossRef] [PubMed]
    [Google Scholar]
  23. Grahame-Clarke C. . ( 2005; ). Human cytomegalovirus, endothelial function and atherosclerosis. . Herpes 12:, 42–45.[PubMed]
    [Google Scholar]
  24. Hamirally S. , Kamil J. P. , Ndassa-Colday Y. M. , Lin A. J. , Jahng W. J. , Baek M.-C. , Noton S. , Silva L. A. , Simpson-Holley M. . & other authors ( 2009; ). Viral mimicry of Cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear lamina during human cytomegalovirus nuclear egress. . PLoS Pathog 5:, e1000275. [CrossRef] [PubMed]
    [Google Scholar]
  25. He Z. , He Y. S. , Kim Y. , Chu L. , Ohmstede C. , Biron K. K. , Coen D. M. . ( 1997; ). The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines. . J Virol 71:, 405–411.[PubMed]
    [Google Scholar]
  26. Hertel L. , Mocarski E. S. . ( 2004; ). Global analysis of host cell gene expression late during cytomegalovirus infection reveals extensive dysregulation of cell cycle gene expression and induction of pseudomitosis independent of US28 function. . J Virol 78:, 11988–12011. [CrossRef] [PubMed]
    [Google Scholar]
  27. Hertel L. , Chou S. , Mocarski E. S. . ( 2007; ). Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication. . PLoS Pathog 3:, e6. [CrossRef] [PubMed]
    [Google Scholar]
  28. Hume A. J. , Finkel J. S. , Kamil J. P. , Coen D. M. , Culbertson M. R. , Kalejta R. F. . ( 2008; ). Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. . Science 320:, 797–799. [CrossRef] [PubMed]
    [Google Scholar]
  29. Jault F. M. , Jault J. M. , Ruchti F. , Fortunato E. A. , Clark C. , Corbeil J. , Richman D. D. , Spector D. H. . ( 1995; ). Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. . J Virol 69:, 6697–6704.[PubMed]
    [Google Scholar]
  30. Kalejta R. F. . ( 2008a; ). Functions of human cytomegalovirus tegument proteins prior to immediate early gene expression. . Curr Top Microbiol Immunol 325:, 101–115. [CrossRef] [PubMed]
    [Google Scholar]
  31. Kalejta R. F. . ( 2008b; ). Tegument proteins of human cytomegalovirus. . Microbiol Mol Biol Rev 72:, 249–265. [CrossRef] [PubMed]
    [Google Scholar]
  32. Kalejta R. F. , Bechtel J. T. , Shenk T. . ( 2003; ). Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependent degradation of the retinoblastoma family of tumor suppressors. . Mol Cell Biol 23:, 1885–1895. [CrossRef] [PubMed]
    [Google Scholar]
  33. Kamil J. P. , Coen D. M. . ( 2007; ). Human cytomegalovirus protein kinase UL97 forms a complex with the tegument phosphoprotein pp65. . J Virol 81:, 10659–10668. [CrossRef] [PubMed]
    [Google Scholar]
  34. Kawaguchi Y. , Kato K. . ( 2003; ). Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2. . Rev Med Virol 13:, 331–340. [CrossRef] [PubMed]
    [Google Scholar]
  35. Kawaguchi Y. , Kato K. , Tanaka M. , Kanamori M. , Nishiyama Y. , Yamanashi Y. . ( 2003; ). Conserved protein kinases encoded by herpesviruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1δ. . J Virol 77:, 2359–2368. [CrossRef] [PubMed]
    [Google Scholar]
  36. Krosky P. M. , Baek M.-C. , Coen D. M. . ( 2003a; ). The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. . J Virol 77:, 905–914. [CrossRef] [PubMed]
    [Google Scholar]
  37. Krosky P. M. , Baek M.-C. , Jahng W. J. , Barrera I. , Harvey R. J. , Biron K. K. , Coen D. M. , Sethna P. B. . ( 2003b; ). The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. . J Virol 77:, 7720–7727. [CrossRef] [PubMed]
    [Google Scholar]
  38. Kuny C. V. , Chinchilla K. , Culbertson M. R. , Kalejta R. F. . ( 2010; ). Cyclin-dependent kinase-like function is shared by the beta- and gamma- subset of the conserved herpesvirus protein kinases. . PLoS Pathog 6:, e1001092. [CrossRef] [PubMed]
    [Google Scholar]
  39. Kushnir A. S. , Davido D. J. , Schaffer P. A. . ( 2010; ). Role of nuclear factor Y in stress-induced activation of the herpes simplex virus type 1 ICP0 promoter. . J Virol 84:, 188–200. [CrossRef] [PubMed]
    [Google Scholar]
  40. Lee K. S. , Asano S. , Park J.-E. , Sakchaisri K. , Erikson R. L. . ( 2005; ). Monitoring the cell cycle by multi-kinase-dependent regulation of Swe1/Wee1 in budding yeast. . Cell Cycle 4:, 1346–1349. [CrossRef] [PubMed]
    [Google Scholar]
  41. Lee C.-P. , Huang Y.-H. , Lin S.-F. , Chang Y. , Chang Y.-H. , Takada K. , Chen M.-R. . ( 2008; ). Epstein–Barr virus BGLF4 kinase induces disassembly of the nuclear lamina to facilitate virion production. . J Virol 82:, 11913–11926. [CrossRef] [PubMed]
    [Google Scholar]
  42. Lindqvist A. , Rodríguez-Bravo V. , Medema R. H. . ( 2009; ). The decision to enter mitosis: feedback and redundancy in the mitotic entry network. . J Cell Biol 185:, 193–202. [CrossRef] [PubMed]
    [Google Scholar]
  43. Liu H. , Bird R. C. . ( 1998; ). Characterization of the enhancer-like okadaic acid response element region of the cyclin-dependent kinase 1 (p34cdc2) promoter. . Biochem Biophys Res Commun 246:, 696–702. [CrossRef] [PubMed]
    [Google Scholar]
  44. Liu J. , Kipreos E. T. . ( 2000; ). Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa. . Mol Biol Evol 17:, 1061–1074. [CrossRef] [PubMed]
    [Google Scholar]
  45. Lu M. , Shenk T. . ( 1996; ). Human cytomegalovirus infection inhibits cell cycle progression at multiple points, including the transition from G1 to S. . J Virol 70:, 8850–8857.[PubMed]
    [Google Scholar]
  46. Manni I. , Mazzaro G. , Gurtner A. , Mantovani R. , Haugwitz U. , Krause K. , Engeland K. , Sacchi A. , Soddu S. , Piaggio G. . ( 2001; ). NF-Y mediates the transcriptional inhibition of the cyclin B1, cyclin B2, and cdc25C promoters upon induced G2 arrest. . J Biol Chem 276:, 5570–5576. [CrossRef] [PubMed]
    [Google Scholar]
  47. Marschall M. , Stein-Gerlach M. , Freitag M. , Kupfer R. , van den Bogaard M. , Stamminger T. . ( 2001; ). Inhibitors of human cytomegalovirus replication drastically reduce the activity of the viral protein kinase pUL97. . J Gen Virol 82:, 1439–1450.[PubMed]
    [Google Scholar]
  48. Marschall M. , Stein-Gerlach M. , Freitag M. , Kupfer R. , van den Bogaard M. , Stamminger T. . ( 2002; ). Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase inhibitors is a novel principle for antiviral therapy. . J Gen Virol 83:, 1013–1023.[PubMed]
    [Google Scholar]
  49. Marschall M. , Freitag M. , Suchy P. , Romaker D. , Kupfer R. , Hanke M. , Stamminger T. . ( 2003; ). The protein kinase pUL97 of human cytomegalovirus interacts with and phosphorylates the DNA polymerase processivity factor pUL44. . Virology 311:, 60–71. [CrossRef] [PubMed]
    [Google Scholar]
  50. Marschall M. , Marzi A. , aus dem Siepen P. , Jochmann R. , Kalmer M. , Auerochs S. , Lischka P. , Leis M. , Stamminger T. . ( 2005; ). Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina. . J Biol Chem 280:, 33357–33367. [CrossRef] [PubMed]
    [Google Scholar]
  51. Michaelis M. , Doerr H. W. , Cinatl J. . ( 2009; ). The story of human cytomegalovirus and cancer: increasing evidence and open questions. . Neoplasia 11:, 1–9.[PubMed] [CrossRef]
    [Google Scholar]
  52. Michel D. , Pavić I. , Zimmermann A. , Haupt E. , Wunderlich K. , Heuschmid M. , Mertens T. . ( 1996; ). The UL97 gene product of human cytomegalovirus is an early-late protein with a nuclear localization but is not a nucleoside kinase. . J Virol 70:, 6340–6346.[PubMed]
    [Google Scholar]
  53. Miyazaki T. , Arai S. . ( 2007; ). Two distinct controls of mitotic cdk1/cyclin B1 activity requisite for cell growth prior to cell division. . Cell Cycle 6:, 1418–1425. [CrossRef] [PubMed]
    [Google Scholar]
  54. Ogg S. C. , Lamond A. I. . ( 2002; ). Cajal bodies and coilin – moving towards function. . J Cell Biol 159:, 17–21. [CrossRef] [PubMed]
    [Google Scholar]
  55. Onishi T. , Zhang W. , Cao X. , Hruska K. . ( 1997; ). The mitogenic effect of parathyroid hormone is associated with E2F-dependent activation of cyclin-dependent kinase 1 (cdc2) in osteoblast precursors. . J Bone Miner Res 12:, 1596–1605. [CrossRef] [PubMed]
    [Google Scholar]
  56. Padmanabhan R. , Tanimoto A. , Sasaguri Y. . ( 2003; ). Transactivation of human cdc2 promoter by adenovirus E1A. . Curr Top Microbiol Immunol 272:, 365–397.[PubMed]
    [Google Scholar]
  57. Pfaffl M. W. . ( 2001; ). A new mathematical model for relative quantification in real-time RT-PCR. . Nucleic Acids Res 29:, e45. [CrossRef] [PubMed]
    [Google Scholar]
  58. Prichard M. N. . ( 2009; ). Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir. . Rev Med Virol 19:, 215–229. [CrossRef] [PubMed]
    [Google Scholar]
  59. Prichard M. N. , Gao N. , Jairath S. , Mulamba G. , Krosky P. , Coen D. M. , Parker B. O. , Pari G. S. . ( 1999; ). A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. . J Virol 73:, 5663–5670.[PubMed]
    [Google Scholar]
  60. Prichard M. N. , Britt W. J. , Daily S. L. , Hartline C. B. , Kern E. R. . ( 2005; ). Human cytomegalovirus UL97 kinase is required for the normal intranuclear distribution of pp65 and virion morphogenesis. . J Virol 79:, 15494–15502. [CrossRef] [PubMed]
    [Google Scholar]
  61. Prichard M. N. , Keith K. A. , Quenelle D. C. , Kern E. R. . ( 2006; ). Activity and mechanism of action of N-methanocarbathymidine against herpesvirus and orthopoxvirus infections. . Antimicrob Agents Chemother 50:, 1336–1341. [CrossRef] [PubMed]
    [Google Scholar]
  62. Prichard M. N. , Sztul E. , Daily S. L. , Perry A. L. , Frederick S. L. , Gill R. B. , Hartline C. B. , Streblow D. N. , Varnum S. M. . & other authors ( 2008; ). Human cytomegalovirus UL97 kinase activity is required for the hyperphosphorylation of retinoblastoma protein and inhibits the formation of nuclear aggresomes. . J Virol 82:, 5054–5067. [CrossRef] [PubMed]
    [Google Scholar]
  63. Rechter S. , Scott G. M. , Eickhoff J. , Zielke K. , Auerochs S. , Müller R. , Stamminger T. , Rawlinson W. D. , Marschall M. . ( 2009; ). Cyclin-dependent kinases phosphorylate the cytomegalovirus RNA export protein pUL69 and modulate its nuclear localization and activity. . J Biol Chem 284:, 8605–8613. [CrossRef] [PubMed]
    [Google Scholar]
  64. Reeves M. , Sinclair J. . ( 2008; ). Aspects of human cytomegalovirus latency and reactivation. . Curr Top Microbiol Immunol 325:, 297–313. [CrossRef] [PubMed]
    [Google Scholar]
  65. Rybak R. J. , Hartline C. B. , Qiu Y.-L. , Zemlicka J. , Harden E. , Marshall G. , Sommadossi J.-P. , Kern E. R. . ( 2000; ). In vitro activities of methylenecyclopropane analogues of nucleosides and their phosphoralaninate prodrugs against cytomegalovirus and other herpesvirus infections. . Antimicrob Agents Chemother 44:, 1506–1511. [CrossRef] [PubMed]
    [Google Scholar]
  66. Salvant B. S. , Fortunato E. A. , Spector D. H. . ( 1998; ). Cell cycle dysregulation by human cytomegalovirus: influence of the cell cycle phase at the time of infection and effects on cyclin transcription. . J Virol 72:, 3729–3741.[PubMed]
    [Google Scholar]
  67. Sanchez V. , Greis K. D. , Sztul E. , Britt W. J. . ( 2000; ). Accumulation of virion tegument and envelope proteins in a stable cytoplasmic compartment during human cytomegalovirus replication: characterization of a potential site of virus assembly. . J Virol 74:, 975–986. [CrossRef] [PubMed]
    [Google Scholar]
  68. Sanchez V. , McElroy A. K. , Spector D. H. . ( 2003; ). Mechanisms governing maintenance of Cdk1/cyclin B1 kinase activity in cells infected with human cytomegalovirus. . J Virol 77:, 13214–13224. [CrossRef] [PubMed]
    [Google Scholar]
  69. Sanchez V. , Mahr J. A. , Orazio N. I. , Spector D. H. . ( 2007; ). Nuclear export of the human cytomegalovirus tegument protein pp65 requires cyclin-dependent kinase activity and the Crm1 exporter. . J Virol 81:, 11730–11736. [CrossRef] [PubMed]
    [Google Scholar]
  70. Schmolke S. , Drescher P. , Jahn G. , Plachter B. . ( 1995; ). Nuclear targeting of the tegument protein pp65 (UL83) of human cytomegalovirus: an unusual bipartite nuclear localization signal functions with other portions of the protein to mediate its efficient nuclear transport. . J Virol 69:, 1071–1078.[PubMed]
    [Google Scholar]
  71. Smith-Donald B. A. , Durand L. O. , Roizman B. . ( 2008; ). Role of cellular phosphatase cdc25C in herpes simplex virus 1 replication. . J Virol 82:, 4527–4532. [CrossRef] [PubMed]
    [Google Scholar]
  72. Stenberg R. M. , Depto A. S. , Fortney J. , Nelson J. A. . ( 1989; ). Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate-early gene region. . J Virol 63:, 2699–2708.[PubMed]
    [Google Scholar]
  73. Thomas M. , Rechter S. , Milbradt J. , Auerochs S. , Müller R. , Stamminger T. , Marschall M. . ( 2009; ). Cytomegaloviral protein kinase pUL97 interacts with the nuclear mRNA export factor pUL69 to modulate its intranuclear localization and activity. . J Gen Virol 90:, 567–578. [CrossRef] [PubMed]
    [Google Scholar]
  74. Tran K. , Kamil J. P. , Coen D. M. , Spector D. H. . ( 2010; ). Inactivation and disassembly of the anaphase-promoting complex during human cytomegalovirus infection is associated with degradation of the APC5 and APC4 subunits and does not require UL97-mediated phosphorylation of Cdh1. . J Virol 84:, 10832–10843. [CrossRef] [PubMed]
    [Google Scholar]
  75. van Zeijl M. , Fairhurst J. , Baum E. Z. , Sun L. , Jones T. R. . ( 1997; ). The human cytomegalovirus UL97 protein is phosphorylated and a component of virions. . Virology 231:, 72–80. [CrossRef] [PubMed]
    [Google Scholar]
  76. Varnum S. M. , Streblow D. N. , Monroe M. E. , Smith P. , Auberry K. J. , Pasa-Tolic L. , Wang D. , Camp D. G. II , Rodland K. . & other authors ( 2004; ). Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. . J Virol 78:, 10960–10966. [CrossRef] [PubMed]
    [Google Scholar]
  77. Webel R. , Milbradt J. , Auerochs S. , Schregel V. , Held C. , Nöbauer K. , Razzazi-Fazeli E. , Jardin C. , Wittenberg T. . & other authors ( 2011; ). Two isoforms of the protein kinase pUL97 of human cytomegalovirus are differentially regulated in their nuclear translocation. . J Gen Virol 92:, 638–649. [CrossRef] [PubMed]
    [Google Scholar]
  78. Williams S. L. , Hartline C. B. , Kushner N. L. , Harden E. A. , Bidanset D. J. , Drach J. C. , Townsend L. B. , Underwood M. R. , Biron K. K. , Kern E. R. . ( 2003; ). In vitro activities of benzimidazole d- and l-ribonucleosides against herpesviruses. . Antimicrob Agents Chemother 47:, 2186–2192. [CrossRef] [PubMed]
    [Google Scholar]
  79. Williams-Aziz S. L. , Hartline C. B. , Harden E. A. , Daily S. L. , Prichard M. N. , Kushner N. L. , Beadle J. R. , Wan W. B. , Hostetler K. Y. , Kern E. R. . ( 2005; ). Comparative activities of lipid esters of cidofovir and cyclic cidofovir against replication of herpesviruses in vitro. . Antimicrob Agents Chemother 49:, 3724–3733. [CrossRef] [PubMed]
    [Google Scholar]
  80. Wolf D. G. , Courcelle C. T. , Prichard M. N. , Mocarski E. S. . ( 2001; ). Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. . Proc Natl Acad Sci U S A 98:, 1895–1900. [CrossRef] [PubMed]
    [Google Scholar]
  81. You J. , Bird R. C. . ( 1995; ). Selective induction of cell cycle regulatory genes cdk1 (p34cdc2), cyclins A/B, and the tumor suppressor gene Rb in transformed cells by okadaic acid. . J Cell Physiol 164:, 424–433. [CrossRef] [PubMed]
    [Google Scholar]
  82. Yun J. , Chae H.-D. , Choi T.-S. , Kim E.-H. , Bang Y.-J. , Chung J. , Choi K.-S. , Mantovani R. , Shin D. Y. . ( 2003; ). Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53–p21 signaling pathway. . J Biol Chem 278:, 36966–36972. [CrossRef] [PubMed]
    [Google Scholar]
  83. Zimmermann A. , Wilts H. , Lenhardt M. , Hahn M. , Mertens T. . ( 2000; ). Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase. . Antiviral Res 48:, 49–60. [CrossRef] [PubMed]
    [Google Scholar]
  84. Zydek M. , Hagemeier C. , Wiebusch L. . ( 2010; ). Cyclin-dependent kinase activity controls the onset of the HCMV lytic cycle. . PLoS Pathog 6:, e1001096. [CrossRef] [PubMed]
    [Google Scholar]
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