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The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation

Gardiol, Daniela, Kühne, Christian, Glaunsinger, Britt, Lee, Siu Sylvia, Javier, Ron, Banks, Lawrence·1999·Oncogene
DOI 10.1038/sj.onc.1202920
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Abstract

Previous studies have shown that the oncogenic HPV E6 proteins form a complex with the human homologue of the Drosophila tumour suppressor protein, discs large (Dlg). This is mediated by the carboxy terminus of the E6 proteins and involves recognition of at least one PDZ domain of Dlg. This region of E6 is not conserved amongst E6 proteins from the low risk papillomavirus types and, hence, binding of HPV E6 proteins to Dlg correlates with the oncogenic potential of these viruses. We have performed studies to investigate the consequences of the interaction between E6 and Dlg. Mutational analysis of both the HPV18 E6 and Dlg proteins has further defined the regions of E6 and Dlg necessary for complex formation. Strikingly, co-expression of wild type HPV18 E6 with Dlg in vitro or in vivo results in a dramatic decrease in the amount of Dlg protein, whereas mutants of E6 which fail to complex with Dlg have minimal effect on Dlg protein levels. The oncogenic HPV16 E6 also decreased the Dlg levels, but this was not observed with the low risk HPV11 E6 protein. Moreover, a region within the first 544 amino acids of Dlg containing the three PDZ domains confers susceptibility to E6 mediated degradation. Finally, treatment of cells with a proteasome inhibitor overrides the capacity of E6 to degrade Dlg. These results demonstrate that Dlg is targeted by high risk HPV E6 proteins for proteasome mediated degradation.

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Crossref · 10.1038/sj.onc.1202920

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Research works printed but not linked: 35

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Cited by

Metadata

Authors
Gardiol, D., Kühne, C., Glaunsinger, B., Lee, S. S., Javier, R., & Banks, L.
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
1999-09-30
Volume
18
Issue
40
Pages
5487-5496
ISSN
  • 0950-9232
  • 1476-5594
DOI
10.1038/sj.onc.1202920
Cited by
277
References
2
Language
en
Licence

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