Cross Talk between eIF2α and eEF2 Phosphorylation Pathways Optimizes Translational Arrest in Response to Oxidative Stress.

ABSTRACT: 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 ac

SUBMITTER: Sanchez M 

PROVIDER: S-EPMC6823656 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature