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The stability of the human papillomavirus E6 oncoprotein is E6AP dependent
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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“The E6–E6AP complex has also been shown to be important for E6 stability, and the ablation of E6AP thus rescues p53 through two routes: as a result of E6 destabilization and the loss of E6AP ubiquitin ligase activity [173,174]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [174]
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Research works printed but not linked: 25
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Cited by
Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Self-citation
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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