ArticlePloS one2015
Phosphorylation of eIF4E Confers Resistance to Cellular Stress and DNA-Damaging Agents through an Interaction with 4E-T: A Rationale for Novel Therapeutic Approaches.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- The many ways to inhibit translation by Sorafenib in liver cancer cells.Molecular and cellular biochemistry · 2026Article
- eIF4E orchestrates mRNA processing, RNA export and translation to modify specific protein production.Nucleus (Austin, Tex.) · 2024Review
- PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation.Life science alliance · 2024Article
- Article
- Cell death or survival: Insights into the role of mRNA translational control.Seminars in cell & developmental biology · 2024Review
- Stress-Induced Eukaryotic Translational Regulatory Mechanisms.Journal of clinical and medical sciences · 2024Article
- Inhibition of casein kinase 2 sensitizes mantle cell lymphoma to venetoclax through MCL-1 downregulation.Haematologica · 2023Article
- Protective Effects of Recombinant Human Angiogenin in Keratinocytes: New Insights on Oxidative Stress Response Mediated by RNases.International journal of molecular sciences · 2022Article
- Post-transcriptional regulation during stress.FEMS yeast research · 2022Review
- Comprehensive analysis of expression, prognosis and immune infiltration for TIMPs in glioblastoma.BMC neurology · 2021Article
- Synthetic Retinoids as Potential Therapeutics in Prostate Cancer-An Update of the Last Decade of Research: A Review.International journal of molecular sciences · 2021Review
- Clinical implications of intratumor heterogeneity: challenges and opportunities.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Understanding the roles of stress granule during chemotherapy for patients with malignant tumors.American journal of cancer research · 2020Review
- Integrating clinical, molecular, proteomic and histopathological data within the tissue context: tissunomics.Histopathology · 2019Review
- Review
- Inhibiting ERK/Mnk/eIF4E broadly sensitizes ovarian cancer response to chemotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Article
- Revealing the Determinants of Widespread Alternative Splicing Perturbation in Cancer.Cell reports · 2017Article
- The MNK-eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Macrophages confer survival signals via CCR1-dependent translational MCL-1 induction in chronic lymphocytic leukemia.Oncogene · 2017Article
- Targeting the eIF4E/β-catenin axis sensitizes cervical carcinoma squamous cells to chemotherapy.American journal of translational research · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation of the eukaryotic translation initiation factor eIF4E is associated with malignant progression and poor cancer prognosis. Accordingly, here we have analyzed the association between eIF4E phosphorylation and cellular resistance to oxidative stress, starvation, and DNA-damaging agents in vitro. Using immortalized and cancer cell lines, retroviral expression of a phosphomimetic (S209D) form of eIF4E, but not phospho-dead (S209A) eIF4E or GFP control, significantly increased cellular resistance to stress induced by DNA-damaging agents (cisplatin), starvation (glucose+glutamine withdrawal), and oxidative stress (arsenite). De novo accumulation of eIF4E-containing cytoplasmic bodies colocalizing with the eIF4E-binding protein 4E-T was observed after expression of phosphomimetic S209D, but not S209A or wild-type eIF4E. Increased resistance to cellular stress induced by eIF4E-S209D was lost upon knockdown of endogenous 4E-T or use of an eIF4E-W73A-S209D mutant unable to bind 4E-T. Cancer cells treated with the Mnk1/2 inhibitor CGP57380 to prevent eIF4E phosphorylation and mouse embryonic fibroblasts derived from Mnk1/2 knockout mice were also more sensitive to arsenite and cisplatin treatment. Polysome analysis revealed an 80S peak 2 hours after arsenite treatment in cells overexpressing phosphomimetic eIF4E, indicating translational stalling. Nonetheless, a selective increase was observed in the synthesis of some proteins (cyclin D1, HuR, and Mcl-1). We conclude that phosphorylation of eIF4E confers resistance to various cell stressors and that a direct interaction or regulation of 4E-T by eIF4E is required. Further delineation of this process may identify novel therapeutic avenues for cancer treatment, and these results support the use of modern Mnk1/2 inhibitors in conjunction with standard therapy.
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