1887

Abstract

An important characteristic of the E6 proteins derived from cancer-associated human papillomaviruses (HPVs) is their ability to target cellular proteins for ubiquitin-mediated degradation. Degradation of the p53 tumour suppressor protein by E6 is known to involve the cellular ubiquitin ligase, E6-AP; however, it is presently not known how E6 targets the discs large (Dlg) tumour suppressor and the membrane-associated guanylate kinase inverted (MAGI) family of proteins for degradation. By using an E6-AP immunodepletion assay, these targets were tested for degradation in a E6-AP-dependent manner. The data showed clearly that E6 can direct the degradation of Dlg and the MAGI family of proteins in the absence of E6-AP in this system. These results provide compelling evidence for the role of E6-associated ubiquitin ligases other than E6-AP in the degradation of certain E6 targets.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80035-0
2004-10-01
2020-04-08
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/10/vir852815.html?itemId=/content/journal/jgv/10.1099/vir.0.80035-0&mimeType=html&fmt=ahah

References

  1. Ciechanover A. 1998; The ubiquitin–proteasome pathway: on protein death and cell life. EMBO J 17:7151–7160 [CrossRef]
    [Google Scholar]
  2. Ciechanover A., Orian A., Schwartz A. L. 2000; Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays 22:442–451 [CrossRef]
    [Google Scholar]
  3. Gardiol D., Kühne C., Glaunsinger B., Lee S. S., Javier R., Banks L. 1999; Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 18:5487–5496 [CrossRef]
    [Google Scholar]
  4. Glaunsinger B. A., Lee S. S., Thomas M., Banks L., Javier R. 2000; Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins. Oncogene 19:5270–5280 [CrossRef]
    [Google Scholar]
  5. Haupt Y., Maya R., Kazaz A., Oren M. 1997; Mdm2 promotes the rapid degradation of p53. Nature 387:296–299 [CrossRef]
    [Google Scholar]
  6. Hengstermann A., Linares L. K., Ciechanover A., Whitaker N. J., Scheffner M. 2001; Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells. Proc Natl Acad Sci U S A 98:1218–1223 [CrossRef]
    [Google Scholar]
  7. Huibregtse J. M., Scheffner M., Howley P. M. 1991; A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J 10:4129–4135
    [Google Scholar]
  8. Huibregtse J. M., Scheffner M., Howley P. M. 1993; Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol Cell Biol 13:775–784
    [Google Scholar]
  9. Huibregtse J. M., Scheffner M., Beaudenon S., Howley P. M. 1995; A family of proteins structurally and functionally related to the E6-AP ubiquitin–protein ligase. Proc Natl Acad Sci U S A 92:2563–2567 [CrossRef]
    [Google Scholar]
  10. Kim S. K. 1997; Polarized signaling: basolateral receptor localization in epithelial cells by PDZ-containing proteins. Curr Opin Cell Biol 9:853–859 [CrossRef]
    [Google Scholar]
  11. Kubbutat M. H., Jones S. N., Vousden K. H. 1997; Regulation of p53 stability by Mdm2. Nature 387:299–303 [CrossRef]
    [Google Scholar]
  12. Li X., Coffino P. 1996; High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation. J Virol 70:4509–4516
    [Google Scholar]
  13. Mantovani F., Banks L. 2001; The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20:7874–7887 [CrossRef]
    [Google Scholar]
  14. Mantovani F., Massimi P., Banks L. 2001; Proteasome-mediated regulation of the hDlg tumour suppressor protein. J Cell Sci 114:4285–4292
    [Google Scholar]
  15. Nakagawa S., Huibregtse J. M. 2000; Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 20:8244–8253 [CrossRef]
    [Google Scholar]
  16. Pim D., Thomas M., Javier R., Gardiol D., Banks L. 2000; HPV E6 targeted degradation of the discs large protein: evidence for the involvement of a novel ubiquitin ligase. Oncogene 19:719–725 [CrossRef]
    [Google Scholar]
  17. Pim D., Thomas M., Banks L. 2002; Chimaeric HPV E6 proteins allow dissection of the proteolytic pathways regulating different E6 cellular target proteins. Oncogene 21:8140–8148 [CrossRef]
    [Google Scholar]
  18. Rolfe M., Beer-Romero P., Glass S., Eckstein J., Berdo I., Theodoras A., Pagano M., Draetta G. 1995; Reconstitution of p53–ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP). Proc Natl Acad Sci U S A 92:3264–3268 [CrossRef]
    [Google Scholar]
  19. Scheffner M., Werness B. A., Huibregtse J. M., Levine A. J., Howley P. M. 1990; The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136 [CrossRef]
    [Google Scholar]
  20. Scheffner M., Huibregtse J. M., Vierstra R. D., Howley P. M. 1993; The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75:495–505 [CrossRef]
    [Google Scholar]
  21. Scheffner M., Huibregtse J. M., Howley P. M. 1994; Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53. Proc Natl Acad Sci U S A 91:8797–8801 [CrossRef]
    [Google Scholar]
  22. Scheffner M., Nuber U., Huibregtse J. M. 1995; Protein ubiquitination involving an E1–E2–E3 enzyme ubiquitin thioester cascade. Nature 373:81–83 [CrossRef]
    [Google Scholar]
  23. Sterlinko Grm H., Weber M., Elston R., McIntosh P., Griffin H., Banks L., Doorbar J. 2004; Inhibition of E6-induced degradation of its cellular substrates by novel blocking peptides. J Mol Biol 335:971–985 [CrossRef]
    [Google Scholar]
  24. Thomas M., Glaunsinger B., Pim D., Javier R., Banks L. 2001; HPV E6 and MAGUK protein interactions: determination of the molecular basis for specific protein recognition and degradation. Oncogene 20:5431–5439 [CrossRef]
    [Google Scholar]
  25. Thomas M., Pim D., Banks L. 2002a; Human papillomavirus E6 protein interactions. In Human Papilloma Viruses Perspectives in Medical Virology 8 pp  71–99 Edited by McCance D. J. Amsterdam: Elsevier;
    [Google Scholar]
  26. Thomas M., Laura R., Hepner K., Guccione E., Sawyers C., Lasky L., Banks L. 2002b; Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation. Oncogene 21:5088–5096 [CrossRef]
    [Google Scholar]
  27. Werness B. A., Levine A. J., Howley P. M. 1990; Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248:76–79 [CrossRef]
    [Google Scholar]
  28. zur Hausen H., Schneider A. 1987; The role of papillomaviruses in human anogenital cancer. In The Papillomaviruses pp  245–263 Edited by Salzman N. P., Howley P. M. New York: Plenum;
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80035-0
Loading
/content/journal/jgv/10.1099/vir.0.80035-0
Loading

Data & Media loading...

Most cited this month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error