title: E6 proteins from low-risk human papillomavirus types 6 and 11 are able to protect keratinocytes from apoptosis via Bak degradation.
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.
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.|Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Underbrink
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Dupuis
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Dermatology, University of Texas Health Science Center, Houston, TX 77030, USA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
mesh_terms: D017209:Apoptosis; D052140:Human papillomavirus 11 / Q000235:genetics / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D052163:Human papillomavirus 6 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D059748:Proteolysis; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494772:BAK1 protein, human; D009856:Oncogene Proteins, Viral; D050998:bcl-2 Homologous Antagonist-Killer Protein