E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

Peechanika Chopjitt; Chamsai Pientong; Nuchsupha Sunthamala; Bunkerd Kongyingyoes; Ornuma Haonon; Thidarut Boonmars; Satomi Kikawa; Tomomi Nakahara; Tohru Kiyono; Tipaya Ekalaksananan

doi:10.1016/j.bbrc.2016.07.025

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

Biochem Biophys Res Commun. 2016 Sep 9;478(1):417-423. doi: 10.1016/j.bbrc.2016.07.025. Epub 2016 Jul 5.

Affiliations

¹ Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Thailand.
² Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
³ Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
⁴ Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁵ Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: tkiyono@ncc.go.jp.
⁶ Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Thailand. Electronic address: tipeka@kku.ac.th.

PMID: 27392712
DOI: 10.1016/j.bbrc.2016.07.025

Abstract

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant.

Keywords: E6D25E; E6Pro; HPV16As variant; Human cervical keratinocyte (HCK1T); Protein profile; gp96 (HSP90B1).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Transformation, Viral / immunology*
Cells, Cultured
Cytokines / immunology
Gene Expression Regulation, Viral / immunology
Human papillomavirus 16 / classification
Human papillomavirus 16 / isolation & purification
Human papillomavirus 16 / physiology*
Humans
Immunity, Innate / immunology*
Keratinocytes / immunology*
Keratinocytes / virology*
Proteome / immunology*
Species Specificity

Substances

Cytokines
Proteome