OGFOD1, a novel modulator of eukaryotic translation initiation factor 2α phosphorylation and the cellular response to stress
KA Wehner, S Schütz, P Sarnow - Molecular and cellular biology, 2010 - Taylor & Francis
KA Wehner, S Schütz, P Sarnow
Molecular and cellular biology, 2010•Taylor & FrancisCells possess mechanisms that permit survival and recovery from stress, several of which
regulate the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). We
identified the human OGFOD1 protein as a novel stress granule component that regulates
the phosphorylation of eIF2α and the resumption of translation in cells recovering from
arsenite-induced stress. Coimmunoprecipitation studies revealed that OGFOD1 associates
with a small subset of stress granule proteins (G3BP1, USP10, Caprin1, and YB-1) and the …
regulate the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). We
identified the human OGFOD1 protein as a novel stress granule component that regulates
the phosphorylation of eIF2α and the resumption of translation in cells recovering from
arsenite-induced stress. Coimmunoprecipitation studies revealed that OGFOD1 associates
with a small subset of stress granule proteins (G3BP1, USP10, Caprin1, and YB-1) and the …
Cells possess mechanisms that permit survival and recovery from stress, several of which regulate the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). We identified the human OGFOD1 protein as a novel stress granule component that regulates the phosphorylation of eIF2α and the resumption of translation in cells recovering from arsenite-induced stress. Coimmunoprecipitation studies revealed that OGFOD1 associates with a small subset of stress granule proteins (G3BP1, USP10, Caprin1, and YB-1) and the ribosome in both unstressed and stressed cells. Overexpression of OGFOD1 led to increased abundance of phosphorylated eIF2α, both in unstressed cells and in cells exposed to arsenite-induced stress, and to accelerated apoptosis during stress. Conversely, knockdown of OGFOD1 resulted in smaller amounts of phosphorylated eIF2α and a faster accumulation of polyribosomes in cells recovering from stress. Finally, OGFOD1 interacted with both eIF2α and the eIF2α kinase heme-regulated inhibitor (HRI), which was identified as a novel stress granule resident. These findings argue that OGFOD1 plays important proapoptotic roles in the regulation of translation and HRI-mediated phosphorylation of eIF2α in cells subjected to arsenite-induced stress.
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