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Specific interaction between HPV-16 E1–E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network

Abstract

THE human papillomaviruses (HPV) are associated specifically with epithelial lesions, ranging from benign warts to invasive carcinoma (for review, see refs 1, 2). The virus encodes three late proteins, which are produced only in terminally differentiating keratinocytes, two of which are structural components of the virion3. The third, E1–E4, is derived primarily from the E4 open reading frame, which represents a region of maximal divergence between different HPV types4,5. E1–E4 does not seem to be a component of the virus particle or to be needed for transformation in vitro6,7, but accumulates in the cytoplasm5,8–10, where in certain benign lesions it can comprise 20–30% of total cell protein4,10. We show here that expression of the HPV-16 E1–E4 protein in human keratinocytes (the natural host cell for HPV infection) results in the total collapse of the cytokeratin matrix. Tubulin and actin networks are unaffected by E1–E4, as are the nuclear lamins.

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References

  1. zur Hausen, H. & Schneider, A. in The Papovaviridae (eds Salzman, N. P. & Howley, P. M.) (Plenum, New York, 1990).

    Google Scholar 

  2. Broker, T. R. & Botchan, M. in Cancer Cells 4: DNA Tumour Viruses (eds Botchan, M., Grodzicker, T. & Sharp, P. A.) 17–36 (Cold Spring Harbor Laboratory, New York, 1986).

    Google Scholar 

  3. Doorbar, J. & Gallimore, P. H. J. Virol. 61, 2793–2799 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Doorbar, J., Evans, H. S., Coneron, I., Crawford, L. V. & Gallimore, P. H. EMBO J. 7, 825–833 (1988).

    Article  CAS  Google Scholar 

  5. Doorbar, J., Coneron, I. & Gallimore, P. H. Virology 172, 51–62 (1989).

    Article  CAS  Google Scholar 

  6. Phelps, W. C., Yee, C. L., Munger, K. & Howley, P. M. Cell 53, 539–547 (1988).

    Article  CAS  Google Scholar 

  7. Storey, A. et al. EMBO J. 6, 1815–1820 (1988).

    Article  Google Scholar 

  8. Crum, C. P. et al. Virology 178, 238–246 (1990).

    Article  CAS  Google Scholar 

  9. Brown, D. R., Chin, M. T. & Strike, D. G. Virology 165, 262–267 (1988).

    Article  CAS  Google Scholar 

  10. Breitburd, F., Croissant, O. & Orth, G. in Cancer Cells 5: Papillomaviruses (eds Steinberg. B. M., Brandsma, J. L. & Talchman, L. B.) 115–122 (Cold Spring Harbor Laboratory, New York, 1987).

    Google Scholar 

  11. Mackett, M., Smith, G. L. & Moss, B. in DNA Cloning: A Practical Approach Vol. 2 (ed. Glover, D. M.) (IRL, Oxford, 1985).

    Google Scholar 

  12. Browne, H. M., Churcher, M. J., Stanley, M. A., Smith, G. L. & Minson, A. C. J. gen. Virol. 69, 1263–1273 (1988).

    Article  CAS  Google Scholar 

  13. McLean, C. S. et al. J. clin. Pathol. 43, 488–492 (1990).

    Article  CAS  Google Scholar 

  14. Boukamp, P. et al. J. Cell Biol. 106, 761–771 (1988).

    Article  CAS  Google Scholar 

  15. Taylor-Papadimitriou, J., Purkis, P., Lane, E. B., McKay, I. A. & Chang, S. E. Cell Differ. 11, 169–180 (1982).

    Article  CAS  Google Scholar 

  16. Adams, J. C. & Watt, F. M. J. Cell Biol. 107, 1927–1938 (1988).

    Article  CAS  Google Scholar 

  17. Doorbar, J. et al. Virology 178, 254–262 (1990).

    Article  CAS  Google Scholar 

  18. Seedorf, K., Oltersdorf, T., Krammer, G. & Rowekamp, W. EMBO J. 6, 139–144 (1987).

    Article  CAS  Google Scholar 

  19. Hiller, G., Weber, K., Schneider, L., Parajsz, C. & Jungwirth, C. Virology 98, 142–153 (1979).

    Article  CAS  Google Scholar 

  20. Shyy, T. T., Asch, B. B. & Asch, H. J. Cell Biol. 108, 997–1008 (1989).

    Article  CAS  Google Scholar 

  21. Eckert, B. S., Daley, R. A. & Parysek, L. M. Cold Spring Harb. Symp. quant. Biol. 46, 403–412 (1982).

    Article  Google Scholar 

  22. Lane, E. B. & Alexander, C. M. Semin. Cancer Biol. 1, 165–179 (1990).

    CAS  PubMed  Google Scholar 

  23. White, E. & Cipriani, R. Proc. natn. Acad. Sci. U.S.A. 86, 9886–9890 (1989).

    Article  ADS  CAS  Google Scholar 

  24. White, E. & Cipriani, R. Molec. cell. Biol. 10, 120–130 (1990).

    Article  CAS  Google Scholar 

  25. Foisner, R. & Wiche, G. Curr. Opinions Cell. Biol. 3, 75–81 (1991).

    Article  CAS  Google Scholar 

  26. Liebowitz, D., Kopan, R., Fuchs, E., Sample, J. & Kieff, E. Molec. cell. Biol. 7, 2299–2308 (1987).

    Article  CAS  Google Scholar 

  27. Harlow, E. & Lane, D. Antibodies, A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1988).

    Google Scholar 

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Doorbar, J., Ely, S., Sterling, J. et al. Specific interaction between HPV-16 E1–E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature 352, 824–827 (1991). https://doi.org/10.1038/352824a0

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