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The stability of the human papillomavirus E6 oncoprotein is E6AP dependent

Tomaić, Vjekoslav, Pim, David, Banks, Lawrence·2009·Virology

Abstract

Human papillomavirus (HPV) E6 oncoproteins target numerous cellular proteins for ubiquitin-mediated degradation. In the case of p53 this is mediated by the E6AP ubiquitin ligase. However, there are conflicting reports concerning how central E6AP is to the global function of the HPV-16 and HPV-18 E6 oncoproteins. To investigate this further we have analysed the effects of E6AP removal upon the stability of endogenously expressed E6 protein. We show that when E6AP is silenced in HPV-positive cells, E6 protein levels are dramatically decreased in a proteasome-dependent manner. Further, we show that when E6AP is depleted in HeLa cells, E6 has a greatly decreased half-life. In addition, overexpression of E6AP stabilises ectopically expressed HPV-16 and HPV-18 E6 in a manner that is independent of its ubiquitin ligase activity. These results demonstrate that the stability of HPV E6 is critically dependent upon the presence of E6AP.

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Crossref · 10.1016/j.virol.2009.07.029

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Research works printed but not linked: 25

  1. Androphy, 1987, Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines, Embo J., 6, 989, 10.1002/j.1460-2075.1987.tb04849.x · DOI
  2. Beer-Romero, 1997, Antisense targeting of E6AP elevates p53 in HPV-infected cells but not in normal cells, Oncogene, 14, 595, 10.1038/sj.onc.1200872 · DOI
  3. Brimer, 2007, Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein, Virology, 358, 303, 10.1016/j.virol.2006.08.038 · DOI · Paper page
  4. Camus, 2007, Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6, Oncogene, 26, 4059, 10.1038/sj.onc.1210188 · DOI
  5. Cavatorta, 2004, Differential expression of the human homologue of drosophila discs large oncosuppressor in histologic samples from human papillomavirus-associated lesions as a marker for progression to malignancy, Int. J. Cancer, 111, 373, 10.1002/ijc.20275 · DOI
  6. Cooper, 1993, p53 antigen in cervical condylomata, intraepithelial neoplasia, and carcinoma: relationship to HPV infection and integration, J. Pathol., 171, 27, 10.1002/path.1711710107 · DOI
  7. Gardiol, 1999, Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation, Oncogene, 18, 5487, 10.1038/sj.onc.1202920 · DOI · Paper page
  8. Grm, 2004, Degradation of hDlg and MAGIs by human papillomavirus E6 is E6-AP-independent, J. Gen. Virol., 85, 2815, 10.1099/vir.0.80035-0 · DOI
  9. Grossman, 1989, Intracellular localization and DNA-binding properties of human papillomavirus type 18 E6 protein expressed with a baculovirus vector, J. Virol., 63, 366, 10.1128/jvi.63.1.366-374.1989 · DOI
  10. Handa, 2007, E6AP-dependent degradation of DLG4/PSD95 by high-risk human papillomavirus type 18 E6 protein, J. Virol., 81, 1379, 10.1128/JVI.01712-06 · DOI
  11. Hengstermann, 2005, Growth suppression induced by downregulation of E6-AP expression in human papillomavirus-positive cancer cell lines depends on p53, J. Virol., 79, 9296, 10.1128/JVI.79.14.9296-9300.2005 · DOI · Paper page
  12. Huibregtse, 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
  13. Kao, 2000, Human papillomavirus type 16 E6 induces self-ubiquitination of the E6AP ubiquitin-protein ligase, J. Virol., 74, 6408, 10.1128/JVI.74.14.6408-6417.2000 · DOI
  14. Kelley, 2005, The global transcriptional effects of the human papillomavirus E6 protein in cervical carcinoma cell lines are mediated by the E6AP ubiquitin ligase, J. Virol., 79, 3737, 10.1128/JVI.79.6.3737-3747.2005 · DOI
  15. Kuballa, 2007, The role of the ubiquitin ligase E6-AP in human papillomavirus E6-mediated degradation of PDZ domain-containing proteins, J. Biol. Chem., 282, 65, 10.1074/jbc.M605117200 · DOI · Paper page
  16. Mantovani, 2001, The human papillomavirus E6 protein and its contribution to malignant progression, Oncogene, 20, 7874, 10.1038/sj.onc.1204869 · DOI
  17. Massimi, 2008, HPV E6 degradation of p53 and PDZ containing substrates in an E6AP null background, Oncogene, 27, 1800, 10.1038/sj.onc.1210810 · DOI
  18. Munger, 2001, Biological activities and molecular targets of the human papillomavirus E7 oncoprotein, Oncogene, 20, 7888, 10.1038/sj.onc.1204860 · DOI
  19. Pim, 1994, Mutational analysis of HPV-18 E6 identifies domains required for p53 degradation in vitro, abolition of p53 transactivation in vivo and immortalisation of primary BMK cells, Oncogene, 9, 1869
  20. Scheffner, 1993, The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53, Cell, 75, 495, 10.1016/0092-8674(93)90384-3 · DOI · Paper page
  21. Schneider-Gadicke, 1986, Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes, Embo J., 5, 2285, 10.1002/j.1460-2075.1986.tb04496.x · DOI
  22. Shai, 2007, HPV16 E6 confers p53-dependent and p53-independent phenotypes in the epidermis of mice deficient for E6AP, Oncogene, 26, 3321, 10.1038/sj.onc.1210130 · DOI
  23. Storrs, 2007, PATJ, a tight junction-associated PDZ protein, is a novel degradation target of high-risk human papillomavirus E6 and the alternatively spliced isoform 18 E6, J. Virol., 81, 4080, 10.1128/JVI.02545-06 · DOI
  24. Talis, 1998, The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells, J. Biol. Chem., 273, 6439, 10.1074/jbc.273.11.6439 · DOI
  25. Thomas, 1999, The role of the E6–p53 interaction in the molecular pathogenesis of HPV, Oncogene, 18, 7690, 10.1038/sj.onc.1202953 · DOI

Metadata

Authors
Tomaić, V., Pim, D., & Banks, L.
Venue
Virology
Publisher
Elsevier BV
Published
2009-10
Volume
393
Issue
1
Pages
7-10
ISSN
0042-6822
Cited by
76
References
0
Language
en

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Tomaić, V., Pim, D., & Banks, L. (2009). The stability of the human papillomavirus E6 oncoprotein is E6AP dependent. Virology. https://doi.org/10.1016/j.virol.2009.07.029