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 Biojournal_title
FEBS open bioauthors
Morales-Garcia V,Contreras-Paredes A,Martinez-Abundis E,Gomez-Crisostomo NP,Lizano M,Hernandez-Landero F,de la Cruz-Hernandez Edoi
10.1002/2211-5463.12987subject
Has Abstractpub_date
2020-12-01 00:00:00pages
2541-2552issue
12issn
2211-5463journal_volume
10pub_type
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