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PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis

Hatterschide, Joshua, Bohidar, Amelia E., Grace, Miranda, Nulton, Tara J., Kim, Hee Won, Windle, Brad, Morgan, Iain M., Munger, Karl, White, Elizabeth A.·2019·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1819534116

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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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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
DOI
10.1073/pnas.1819534116
Cited by
112
References
9
Language
en
Licence
www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 184 d)
Funders
  • American Cancer Society (131661-RSG-18-048-01-MPC)
  • HHS | NIH | National Cancer Institute (R01 CA066980)

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