E6 proteins from multiple human betapapillomavirus types degrade bak and protect keratinocytes from apoptosis after UVB irradiation

Michael Underbrink, Heather L. Howie, Kristin M. Bedard, Jennifer I. Koop, Denise A. Galloway

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Human papillomavirus (HPV) types from the beta genus (beta-HPVs) have been implicated in the development of skin cancer. A potentially important aspect of their carcinogenic role is the ability of the E6 protein to degrade the proapoptotic family member Bak, which gives cells the ability to survive UV damage. However, it is unknown if the ability to degrade Bak is limited to certain beta-HPV types or whether E6 expression in keratinocytes affects other proteins important for apoptosis signaling. We tested the abilities of E6 proteins from several representative members of the beta-HPVs to degrade Bak and protect UV-treated keratinocytes from apoptosis. The E6 proteins of the beta-HPV type 5 (HPV5), -8, -20, -22, -38, -76, -92, and -96, as well as the alpha genus HPV HPV16, all degraded Bak or prevented its accumulation following UV treatment but did not degrade Bak constitutively. In addition, when tested using HPV16 E6 (16E6) and 8E6 as representative E6 proteins from the alpha and beta genera, respectively, Bak degradation was dependent on the E3 ubiquitin ligase, E6AP. Other important regulators of apoptotic signaling were examined and found to be unperturbed by the expression of the beta-HPV E6 proteins. Importantly, the expression of beta-HPV E6 proteins protected keratinocytes from apoptosis to the same extent as 16E6-expressing cells. In conclusion, several of the beta-HPV types possess the ability to protect UV-treated keratinocytes from apoptosis by reducing levels of Bak in those cells, thus blocking the intrinsic apoptotic pathway.

Original languageEnglish (US)
Pages (from-to)10408-10417
Number of pages10
JournalJournal of Virology
Volume82
Issue number21
DOIs
StatePublished - Nov 2008

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Betapapillomavirus
Papillomaviridae
keratinocytes
Aptitude
Keratinocytes
apoptosis
irradiation
Apoptosis
Proteins
proteins
Ubiquitin-Protein Ligases
Skin Neoplasms
ubiquitin-protein ligase
cells

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

E6 proteins from multiple human betapapillomavirus types degrade bak and protect keratinocytes from apoptosis after UVB irradiation. / Underbrink, Michael; Howie, Heather L.; Bedard, Kristin M.; Koop, Jennifer I.; Galloway, Denise A.

In: Journal of Virology, Vol. 82, No. 21, 11.2008, p. 10408-10417.

Research output: Contribution to journalArticle

Underbrink, Michael ; Howie, Heather L. ; Bedard, Kristin M. ; Koop, Jennifer I. ; Galloway, Denise A. / E6 proteins from multiple human betapapillomavirus types degrade bak and protect keratinocytes from apoptosis after UVB irradiation. In: Journal of Virology. 2008 ; Vol. 82, No. 21. pp. 10408-10417.
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abstract = "Human papillomavirus (HPV) types from the beta genus (beta-HPVs) have been implicated in the development of skin cancer. A potentially important aspect of their carcinogenic role is the ability of the E6 protein to degrade the proapoptotic family member Bak, which gives cells the ability to survive UV damage. However, it is unknown if the ability to degrade Bak is limited to certain beta-HPV types or whether E6 expression in keratinocytes affects other proteins important for apoptosis signaling. We tested the abilities of E6 proteins from several representative members of the beta-HPVs to degrade Bak and protect UV-treated keratinocytes from apoptosis. The E6 proteins of the beta-HPV type 5 (HPV5), -8, -20, -22, -38, -76, -92, and -96, as well as the alpha genus HPV HPV16, all degraded Bak or prevented its accumulation following UV treatment but did not degrade Bak constitutively. In addition, when tested using HPV16 E6 (16E6) and 8E6 as representative E6 proteins from the alpha and beta genera, respectively, Bak degradation was dependent on the E3 ubiquitin ligase, E6AP. Other important regulators of apoptotic signaling were examined and found to be unperturbed by the expression of the beta-HPV E6 proteins. Importantly, the expression of beta-HPV E6 proteins protected keratinocytes from apoptosis to the same extent as 16E6-expressing cells. In conclusion, several of the beta-HPV types possess the ability to protect UV-treated keratinocytes from apoptosis by reducing levels of Bak in those cells, thus blocking the intrinsic apoptotic pathway.",
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