1887

Abstract

Human cytomegalovirus (HCMV) stimulates numerous cellular pathways upon infection. One of these pathways involves activation of cyclin E/Cdk2. Recent reports have demonstrated that Cdk2 is retained in the cytoplasm of cells arrested in G0 by serum deprivation, sequestered from its regulatory subunit cyclin E which is located within the nucleus. Cdk2 rapidly enters the nucleus and becomes active upon stimulation of these cells with serum growth factors. The ability of HCMV to activate cyclin E/Cdk2 in both serum-arrested cells and contact- inhibited cells suggests that HCMV infection may also result in the translocation of Cdk2 into the nucleus. In this report, we demonstrate that Cdk2 is sequestered in the cytoplasm of cells arrested in G0 by contact inhibition, as well as those arrested by serum deprivation. HCMV infection results in translocation of Cdk2 from the cytoplasm into the nucleus within 24 h of infection, both in serum- arrested and contact-inhibited cells.

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1997-08-01
2024-12-13
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References

  1. Albrecht T., Cavallo T., Cole N. L., Graves K. 1980; Cytomegalovirus: development and progression of cytopathic effects in human cell culture. Laboratory Investigation 42:1–7
    [Google Scholar]
  2. Albrecht T., Boldogh I., Fons M., Lee C. H., AbuBakar S., Russell J. M., Au W. W. 1989; Cell-activation responses to cytomegalovirus infection: relationship to the phasing of CMV replication and to the induction of cellular damage. Subcellular Biochemistry 15:157–202
    [Google Scholar]
  3. Albrecht T., Boldogh I., Fons M., AbuBakar S., Deng C. Z. 1990; Cell activation signals and the pathogenesis of human cytomegalovirus. Intervirology 31:68–75
    [Google Scholar]
  4. Alford C. A., Stagno S., Pass R. F., Britt W. 1990; Congenital and perinatal cytomegalovirus infections. Reviews of Infectious Diseases 12:S745–S753
    [Google Scholar]
  5. Baptist M., Lamy F., Gannon J., Hunt T., Dumont J. E., Roger P. P. 1996; Expression and subcellular localization of CDK2 and cdc2 kinases and their common partner cyclin A in thyroid epithelial cells: comparison of cyclic AMP-dependent and -independent cell cycles. Journal of Cellular Physiology 166:256–273
    [Google Scholar]
  6. Boldogh I., AbuBakar S., Albrecht T. 1990; Activation of protooncogenes : an immediate early event in human cytomegalovirus infection. Science 247:961–964
    [Google Scholar]
  7. Bresnahan W. A., Boldogh I., Thompson E. A., Albrecht T. 1996a; Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1. Virology 224:150–160
    [Google Scholar]
  8. Bresnahan W. A., Boldogh I., Ma T., Albrecht T., Thompson E. A. 1996b; Cyclin E/Cdk2 activity is controlled by different mechanisms in the GO and G1 phases of the cell cycle. Cell Growth & Differentiation 7:1283–1290
    [Google Scholar]
  9. DeMarchi J. M. 1983; Correlation between stimulation of host cell DNA synthesis by human cytomegalovirus and lack of expression of a subset of early virus genes. Virology 129:274–286
    [Google Scholar]
  10. Dittmer D., Mocarski E. S. 1997; Human cytomegalovirus infection inhibits Gl/S transition. Journal of Virology 71:1629–1634
    [Google Scholar]
  11. Draetta G. 1994; Mammalian G1 cyclins. Current Opinion in Cell Biology 6:842–846
    [Google Scholar]
  12. Estes J. E., Huang E. -S. 1977; Stimulation of cellular thymidine kinases by human cytomegalovirus. Journal of Virology 24:13–21
    [Google Scholar]
  13. Girard F., Strausfeld U., Fernandez A., Lamb N. 1991; Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67:1169–1179
    [Google Scholar]
  14. Hagemeier C., Walker S. M., Sissons P. J., Sinclair P. H. 1992; The 72K IE1 and 80K IE2 proteins of human cytomegalovirus independently trans-activate the c-fos, c-myc and hsp70 promoters via basal promoter elements. Journal of General Virology 73:2385–2393
    [Google Scholar]
  15. Jault F., Jault J., Ruchti F., Fortunato E., Clark C., Corbeil J., Richman D., Spector D. H. 1995; Cytomegalovirus infection induced high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. Journal of Virology 69:6697–6704
    [Google Scholar]
  16. Lu M., Shenk T. 1996; Human cytomegalovirus infection inhibits cell cycle progression at multiple points, including the transition from G1 to S. Journal of Virology 70:8850–8857
    [Google Scholar]
  17. Monick M. M., Geist L. J., Stinski M. F., Hunninghake G. W. 1992; The immediate early genes of human cytomegalovirus upregulate expression of the cellular genes myc and fos . American Journal ofRespiratory Cell and Molecular Biology 7:251–256
    [Google Scholar]
  18. Resnitzky D., Hengst L., Reed S. 1995; Cyclin A-associated kinase activity is rate limiting for entrance into S phase and is negatively regulatedin G1 by p27Kpi1 . Molecular and Cellular Biology 15:4347–4352
    [Google Scholar]
  19. Rubin R. 1990; Impact of cytomegalovirus infection on organ transplant recipients. Reviews of Infectious Diseases 12:S754–S765
    [Google Scholar]
  20. Schooley R. T. 1990; Cytomegalovirus in the setting ofinfection with human immunodeficiency virus. Reviews of Infectious Diseases 12:S811–S819
    [Google Scholar]
  21. Sherr C. J., Roberts J. M. 1995; Inhibitors of mammalian G cyclin-dependent kinases. Genes & Development 9:1149–1163
    [Google Scholar]
  22. Wade M., Kowalik T. F., Mudryj M., Huang E. -S., Azizkhan J. C. 1992; E2F mediates dihydrofolate reductase promoter activation and multiprotein complex formation in human cytomegalovirus infection. Molecular and Cellular Biology 12:4364–4374
    [Google Scholar]
  23. Weller T. H. 1971; The cytomegaloviruses: ubiquitous agents with protean clinical manifestations. New England Journal of Medicine 285:203–214267–274
    [Google Scholar]
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