Cross Talk between eIF2α and eEF2 Phosphorylation Pathways Optimizes Translational Arrest in Response to Oxidative Stress
| Autor: | Dieter A. Wolf, Philip McQuary, Chih-Cheng Yang, Marisa Sanchez, Alexandre Rosa Campos, Yingying Lin, Pedro Aza Blanc |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
inorganic chemicals 02 engineering and technology EEF2 medicine.disease_cause Article 03 medical and health sciences Molecular Mechanism of Gene Regulation Cellular stress response Protein biosynthesis medicine lcsh:Science Molecular Biology Multidisciplinary Chemistry Kinase Translation (biology) Molecular Microbiology Cell Biology Biological Sciences 021001 nanoscience & nanotechnology Cell biology Elongation factor 030104 developmental biology Phosphorylation lcsh:Q 0210 nano-technology Oxidative stress |
| Zdroj: | iScience, Vol 20, Iss, Pp 466-480 (2019) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary The cellular stress response triggers a cascade of events leading to transcriptional reprogramming and a transient inhibition of global protein synthesis, which is thought to be mediated by phosphorylation of eukaryotic initiation factor-2α (eIF2α). Using mouse embryonic fibroblasts (MEFs) and the fission yeast S. pombe, we report that rapid translational arrest and cell survival in response to hydrogen peroxide-induced oxidative stress do not rely on eIF2α kinases and eIF2α phosphorylation. Rather, H2O2 induces a block in elongation through phosphorylation of eukaryotic elongation factor 2 (eEF2). Kinetic and dose-response analyses uncovered cross talk between the eIF2α and eEF2 phosphorylation pathways, indicating that, in MEFs, eEF2 phosphorylation initiates the acute shutdown in translation, which is maintained by eIF2α phosphorylation. Our results challenge the common conception that eIF2α phosphorylation is the primary trigger of translational arrest in response to oxidative stress and point to integrated control that may facilitate the survival of cancer cells. Graphical Abstract Highlights • Oxidative stress-induced translation arrest is independent of eIF2α phosphorylation • Oxidative stress blocks translation elongation • Oxidative stress triggers eEF2 kinase activation • eEF2K KO cells are hypersensitive to oxidative stress Biological Sciences; Molecular Biology; Molecular Mechanism of Gene Regulation; Molecular Microbiology; Cell Biology |
| Databáze: | OpenAIRE |
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