Human Papillomavirus 16 E6 and E7 Oncoproteins Alter the Abundance of Proteins Associated with DNA Damage Response, Immune Signaling and Epidermal Differentiation.
Cells, Cultured
DNA Damage
Female
Human papillomavirus 16
/ genetics
Humans
Immunity
Infant, Newborn
Inflammation
/ metabolism
Interferons
/ metabolism
Keratinocytes
Oncogene Proteins, Viral
/ genetics
Papillomavirus E7 Proteins
/ genetics
Papillomavirus Infections
/ metabolism
Proteome
/ genetics
Repressor Proteins
E6 protein
E7 protein
human papillomavirus
keratinocytes
proteomics
transformation
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
12 08 2022
12 08 2022
Historique:
received:
19
07
2022
revised:
08
08
2022
accepted:
10
08
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
The high-risk human papillomaviruses are oncogenic viruses associated with almost all cases of cervical carcinomas, and increasing numbers of anal, and oral cancers. Two oncogenic HPV proteins, E6 and E7, are capable of immortalizing keratinocytes and are required for HPV associated cell transformation. Currently, the influence of these oncoproteins on the global regulation of the host proteome is not well defined. Liquid chromatography coupled with quantitative tandem mass spectrometry using isobaric-tagged peptides was used to investigate the effects of the HPV16 oncoproteins E6 and E7 on protein levels in human neonatal keratinocytes (HEKn). Pathway and gene ontology enrichment analyses revealed that the cells expressing the HPV oncoproteins have elevated levels of proteins related to interferon response, inflammation and DNA damage response, while the proteins related to cell organization and epithelial development are downregulated. This study identifies dysregulated pathways and potential biomarkers associated with HPV oncoproteins in primary keratinocytes which may have therapeutic implications. Most notably, DNA damage response pathways, DNA replication, and interferon signaling pathways were affected in cells transduced with HPV16 E6 and E7 lentiviruses. Moreover, proteins associated with cell organization and differentiation were significantly downregulated in keratinocytes expressing HPV16 E6 + E7. High-risk HPV E6 and E7 oncoproteins are necessary for the HPV-associated transformation of keratinocytes. However their influence on the global dysregulation of keratinocyte proteome is not well documented. Here shotgun proteomics using TMT-labeling detected over 2500 significantly dysregulated proteins associated with E6 and E7 expression. Networks of proteins related to interferon response, inflammation and DNA damage repair pathways were altered.
Identifiants
pubmed: 36016386
pii: v14081764
doi: 10.3390/v14081764
pmc: PMC9415472
pii:
doi:
Substances chimiques
E6 protein, Human papillomavirus type 16
0
Oncogene Proteins, Viral
0
Papillomavirus E7 Proteins
0
Proteome
0
Repressor Proteins
0
oncogene protein E7, Human papillomavirus type 16
0
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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