ArticleCell death & disease2015
Phosphorylation of the translation initiation factor eIF2α at serine 51 determines the cell fate decisions of Akt in response to oxidative stress.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
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- Interleukin-6 is critical in the development of pulmonary vascular disease inProceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Roles of the integrated stress response in regulation of inflammatory reactions.Frontiers in immunology · 2026Review
- Tamoxifen modulates nutrition deprivation-induced ER stress through AMPK-mediated ER-phagy in breast cancer cells.Breast cancer research and treatment · 2024Article
- Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.Nature communications · 2024Article
- mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors.Cancer research communications · 2024Article
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- The cGAS-STING/PERK-eIF2α: Individual or Potentially Collaborative Signaling Transduction in Cardiovascular Diseases.International journal of biological sciences · 2024Review
- Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.Metabolism: clinical and experimental · 2023Article
- Ribonucleic Acid-Mediated Control of Protein Translation Under Stress.Antioxidants & redox signaling · 2023Review
- Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD.bioRxiv : the preprint server for biology · 2023Article
- Sex-Specific Effects of Buprenorphine on Endoplasmic Reticulum Stress, Abnormal Protein Accumulation, and Cell Loss After Pediatric Mild Traumatic Brain Injury in Mice.Neurotrauma reports · 2023Article
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- Lack of CFTR alters the ferret pancreatic ductal epithelial secretome and cellular proteome: Implications for exocrine/endocrine signaling.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- mTOR Signaling as a Regulator of Hematopoietic Stem Cell Fate.Stem cell reviews and reports · 2021Review
- Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma.Cellular and molecular life sciences : CMLS · 2021Review
- Crosstalk between endoplasmic reticulum stress and oxidative stress in the progression of diabetic nephropathy.Cell stress & chaperones · 2021Article
- Short and Sweet: Viral 5`-UTR as a Canonical and Non-Canonical Translation Initiation Switch.Journal of cellular immunology · 2021Article
- Polyhexamethylene guanidine phosphate, chloromethylisothiazolinone, and particulate matter are dispensable for stress granule formation in human airway epithelial cells.Animal cells and systems · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphorylation of the α subunit of the translation initiation factor eIF2 at serine 51 (eIF2αP) is a master regulator of cell adaptation to various forms of stress with implications in antitumor treatments with chemotherapeutic drugs. Herein, we demonstrate that genetic loss of the eIF2α kinases PERK and GCN2 or impaired eIF2αP by genetic means renders immortalized mouse fibroblasts as well as human tumor cells increasingly susceptible to death by oxidative stress. We also show that eIF2αP facilitates Akt activation in cells subjected to oxidative insults. However, whereas Akt activation has a pro-survival role in eIF2αP-proficient cells, the lesser amount of activated Akt in eIF2αP-deficient cells promotes death. At the molecular level, we demonstrate that eIF2αP acts through an ATF4-independent mechanism to control Akt activity via the regulation of mTORC1. Specifically, eIF2αP downregulates mTORC1 activity, which in turn relieves the feedback inhibition of PI3K resulting in the upregulation of the mTORC2-Akt arm. Inhibition of mTORC1 by rapamycin restores Akt activity in eIF2αP-deficient cells but renders them highly susceptible to Akt-mediated death by oxidative stress. Our data demonstrate that eIF2αP acts as a molecular switch that dictates either cell survival or death by activated Akt in response to oxidative stress. Hence, we propose that inactivation of eIF2αP may be a suitable approach to unleash the killing power of Akt in tumor cells treated with pro-oxidant drugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.