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Growth Suppression Induced by Downregulation of E6-AP Expression in Human Papillomavirus-Positive Cancer Cell Lines Depends on p53
Abstract
The ubiquitin-protein ligase E6-AP is utilized by the E6 oncoprotein of human papillomaviruses (HPVs) associated with cervical cancer to target the tumor suppressor p53 for degradation. Here, we report that downregulation of E6-AP expression by RNA interference results in both the accumulation of p53 and growth suppression of the HPV-positive cervical cancer cell lines HeLa and SiHa. In addition, HeLa cells, in which p53 expression was suppressed by RNA interference, are significantly less sensitive to the downregulation of E6-AP expression with respect to growth suppression than parental HeLa cells. These data indicate that the anti-growth-suppressive properties of E6-AP in HPV-positive cells depend on its ability to induce p53 degradation.
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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 [173]
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HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
Linares, L. K., Hengstermann, A., Ciechanover, A., Müller, S., & Scheffner, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2030930100 · Cited by 361
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Cited by
Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Sanduja, S., Kaza, V., & Dixon, D. A. (2009) · Aging · doi:10.18632/aging.100086 · Cited by 65
Metadata
- Authors
- Hengstermann, A., D'silva, M. A., Kuballa, P., Butz, K., Hoppe-Seyler, F., & Scheffner, M.
- Affiliations
- Center for Biochemistry, Faculty of Medicine, and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany
- Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-07
- Volume
- 79
- Issue
- 14
- Pages
- 9296-9300
- ISSN
- 0022-538X
- 1098-5514
- Cited by
- 38
- References
- 1
- Language
- en
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- Hengstermann, A., D'silva, M. A., Kuballa, P., Butz, K., Hoppe-Seyler, F., & Scheffner, M. (2005). Growth Suppression Induced by Downregulation of E6-AP Expression in Human Papillomavirus-Positive Cancer Cell Lines Depends on p53. Journal of Virology. https://doi.org/10.1128/jvi.79.14.9296-9300.2005
