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PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis
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Abstract
Significance: Human papillomaviruses (HPV) uncouple proliferation from differentiation to enable virus replication in epithelial cells. HPV E7 proteins are well established to promote proliferation by binding to and inactivating retinoblastoma family proteins and other cell cycle inhibitors. However, mechanisms by which high-risk HPV oncoproteins inhibit differentiation have not been defined. This paper identifies a mechanism by which high-risk HPV E7 inhibit keratinocyte differentiation. The inhibition of differentiation requires degradation of the cellular protein PTPN14 by high-risk HPV E7, and this degradation is related to the ability of high-risk HPV oncoproteins to immortalize keratinocytes and to cause cancer.
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“suggesting that targeting PTPN14 by high-risk E7 through p600 allows E7-expressing cells to survive anoikis and proliferate, irrespective of their anchorage to the basement membrane [206,207]”
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 [206]
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Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Metadata
- Authors
- Hatterschide, J., Bohidar, A. E., Grace, M., Nulton, T. J., Kim, H. W., Windle, B., Morgan, I. M., Munger, K., & White, E. A.
- Affiliations
- Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
- Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111;
- Philips Institute for Oral Health Research, Department of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University School of Dentistry, Richmond, VA 23298
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-03-20
- Volume
- 116
- Issue
- 14
- Pages
- 7033-7042
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 112
- References
- 9
- Language
- en
- Funders
- American Cancer Society (131661-RSG-18-048-01-MPC)
- HHS | NIH | National Cancer Institute (R01 CA066980)
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- Hatterschide, J., Bohidar, A. E., Grace, M., Nulton, T. J., Kim, H. W., Windle, B., Morgan, I. M., Munger, K., & White, E. A. (2019). PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1819534116