E6 proteins from low-risk human papillomavirus types 6 and 11 are able to protect keratinocytes from apoptosis via Bak degradation

Michael Underbrink, Crystal Dupuis, Jia Wang, Stephen K. Tyring

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Infection of epithelial surfaces with low-risk human papillomavirus (HPV) types 6 and 11 causes troublesome clinical diseases, such as recurrent respiratory papillomatosis, that carry a significant cost burden to the healthcare system. Despite this, less has been studied at the molecular level for the low-risk HPV types when compared with their high-risk counterparts. Recent studies have shown the ability of the HPV E6 protein to degrade the pro-apoptotic family member Bak in high-risk and betapapillomavirus HPV types, which confers a cytoprotective advantage on E6-expressing cells. It is unknown whether low-risk E6 expression disrupts the apoptosis pathway and confers a cytoprotective advantage as a result of Bak degradation. We tested the abilities of 6E6 and 11E6 to degrade Bak and protect keratinocytes from UV-initiated apoptosis. Both low-risk 6E6 and 11E6 proteins were able to degrade activated Bak following UV treatment of keratinocytes. The degradation of Bak in 6E6- and 11E6-expressing cells occurred through the proteasomal pathway, and protected them from apoptosis, specifically through the intrinsic pathway to the same extent as their high-risk HPV16 E6 counterpart. In conclusion, we have found a new, critical and conserved function of low-risk HPV E6 proteins, i.e. the ability to degrade Bak, which gives them a cytoprotective advantage over normal, uninfected cells by specifically disrupting the intrinsic pathway of apoptosis.

Original languageEnglish (US)
Pages (from-to)715-724
Number of pages10
JournalJournal of General Virology
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2016

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Human papillomavirus 11
Human papillomavirus 6
Keratinocytes
Apoptosis
Aptitude
Proteins
Betapapillomavirus
Delivery of Health Care
Costs and Cost Analysis

ASJC Scopus subject areas

  • Virology

Cite this

E6 proteins from low-risk human papillomavirus types 6 and 11 are able to protect keratinocytes from apoptosis via Bak degradation. / Underbrink, Michael; Dupuis, Crystal; Wang, Jia; Tyring, Stephen K.

In: Journal of General Virology, Vol. 97, No. 3, 01.03.2016, p. 715-724.

Research output: Contribution to journalArticle

Underbrink, Michael ; Dupuis, Crystal ; Wang, Jia ; Tyring, Stephen K. / E6 proteins from low-risk human papillomavirus types 6 and 11 are able to protect keratinocytes from apoptosis via Bak degradation. In: Journal of General Virology. 2016 ; Vol. 97, No. 3. pp. 715-724.
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