The high-Risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways.,FEBS Open Bio

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The high-Risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-09-27 , DOI: 10.1002/2211-5463.12987
Vicente Morales-Garcia ₁ , Adriana Contreras-Paredes ₂ , Eduardo Martinez-Abundis ₁ , Nancy P Gomez-Crisostomo ₁ , Marcela Lizano _{2,

3} , Fernanda Hernandez-Landero ₁ , Erick de la Cruz-Hernandez ₁

Affiliation

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.

中文翻译：

高危 HPV E6 蛋白通过 MEK/ERK 和 AKT/PKB 途径修饰 eIF4E 蛋白的活性。

先前的研究提出，人乳头瘤病毒 (HPV) E6 癌蛋白通过依赖于 p53 降解的机制来修饰 eIF4E 的转录活性。然而，这些癌蛋白对调节 eIF4E 蛋白活性的途径的影响仍然知之甚少。因此，我们研究了 E6 蛋白调节 eIF4E 蛋白活性及其对靶基因影响的机制。E6 构建体（HPV-6、HPV-16、HPV-18 和 HPV52）的过表达表明 E6 癌蛋白增加了 eIF4E 蛋白（丝氨酸-209）的磷酸化。该结果主要由 4EBP1 蛋白通过 PI3K/AKT 途径磷酸化介导。此外，宫颈癌细胞系中 eIF4E 磷酸化的药理学抑制显着降低了 CCND1 和 ODC1 的蛋白质水平，

更新日期：2020-12-03

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