OGFOD1, a Novel Modulator of Eukaryotic Translation Initiation Factor 2 alpha Phosphorylation and the Cellular Response to Stress

作者：Wehner Karen A; Schuetz Sylvia; Sarnow Peter^*

来源：Molecular and Cellular Biology, 2010, 30(8): 2006-2016.

DOI：10.1128/MCB.01350-09

Cells possess mechanisms that permit survival and recovery from stress, several of which regulate the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha). We identified the human OGFOD1 protein as a novel stress granule component that regulates the phosphorylation of eIF2 alpha 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 eIF2 alpha, 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 eIF2 alpha and a faster accumulation of polyribosomes in cells recovering from stress. Finally, OGFOD1 interacted with both eIF2 alpha and the eIF2 alpha 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 eIF2 alpha in cells subjected to arsenite-induced stress.

• 出版日期2010-4-15