scholarly journals Stress Granule-Inducing Eukaryotic Translation Initiation Factor 4A Inhibitors Block Influenza A Virus Replication

Viruses ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 388 ◽  
Author(s):  
Patrick Slaine ◽  
Mariel Kleer ◽  
Nathan Smith ◽  
Denys Khaperskyy ◽  
Craig McCormick
Keyword(s):  
Influenza A Virus ◽  
Virus Replication ◽  
Translation Initiation ◽  
Influenza A ◽  
Stress Granule ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

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

2010 ◽  
Vol 30 (8) ◽  
pp. 2006-2016 ◽  
Author(s):  
Karen A. Wehner ◽  
Sylvia Schütz ◽  
Peter Sarnow
Keyword(s):  
Translation Initiation ◽  
Stress Granule ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Induced Stress ◽  
Eukaryotic Translation Initiation ◽  
Phosphorylated Eif2α ◽  
In Cells

ABSTRACT 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.

scholarly journals PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation

2019 ◽  
Vol 30 (6) ◽  
pp. 778-793 ◽  
Author(s):  
Nasim Haghandish ◽  
R. Mitchell Baldwin ◽  
Alan Morettin ◽  
Haben Tesfu Dawit ◽  
Hemanta Adhikary ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Stress Granule ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Single Type ◽  
Granule Formation ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Arginine Residues ◽  
Eukaryotic Translation Initiation

Protein arginine methyltransferases (PRMTs) are a family of enzymes that modify proteins by methylating the guanidino nitrogen atoms of arginine residues to regulate cellular processes such as chromatin remodeling, pre-mRNA splicing, and signal transduction. PRMT7 is the single type III PRMT solely capable of arginine monomethylation. To date, other than histone proteins, there are very few identified substrates of PRMT7. We therefore performed quantitative mass spectrometry experiments to identify PRMT7’s interactome and potential substrates to better characterize the enzyme’s biological function(s) in cells. These experiments revealed that PRMT7 interacts with and can methylate eukaryotic translation initiation factor 2 alpha (eIF2α), in vitro and in breast cancer cells. Furthermore, we uncovered a potential regulatory interplay between eIF2α arginine methylation by PRMT7 and stress-induced phosphorylation status of eIF2α at serine 51. Finally, we demonstrated that PRMT7 is required for eIF2α-dependent stress granule formation in the face of various cellular stresses. Altogether, our findings implicate PRMT7 as a novel mediator of eIF2α-dependent cellular stress response pathways.

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