The high-risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways.

Abstract:

:Previous studies have proposed that the human papillomavirus (HPV) E6 oncoproteins modify the transcriptional activity of eIF4E through mechanisms dependent on p53 degradation. However, the effect of these oncoproteins on pathways regulating the activity of the eIF4E protein remains poorly understood. Hence, we investigated the mechanisms whereby E6 proteins regulate the activity of the eIF4E protein and its effect on target genes. Overexpression of E6 constructs (HPV-6, HPV-16, HPV-18, and HPV52) showed that E6 oncoproteins increased phosphorylation of the eIF4E protein (Serine-209). This result was mainly mediated by phosphorylation of the 4EBP1 protein via the PI3K/AKT pathway. Additionally, the pharmacological inhibition of eIF4E phosphorylation in cervical cancer cell lines substantially reduced the protein levels of CCND1 and ODC1, indicating that E6 of the high-risk genotypes may modify protein synthesis of the eIF4E target genes by increasing the activity of the AKT and ERK pathways.

journal_name

FEBS Open Bio

journal_title

FEBS open bio

authors

Morales-Garcia V,Contreras-Paredes A,Martinez-Abundis E,Gomez-Crisostomo NP,Lizano M,Hernandez-Landero F,de la Cruz-Hernandez E

doi

10.1002/2211-5463.12987

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

2541-2552

issue

12

issn

2211-5463

journal_volume

10

pub_type

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