scholarly journals Stress-induced inhibition of translation independently of eIF2  phosphorylation

2015 ◽  
Vol 128 (23) ◽  
pp. 4420-4427 ◽  
Author(s):  
J. H. J. Knutsen ◽  
G. E. Rodland ◽  
C. A. Boe ◽  
T. W. Haland ◽  
P. Sunnerhagen ◽  
...  
Keyword(s):  
Eif2 Phosphorylation

scholarly journals An efficient in vitro translation system from mammalian cells lacking the translational inhibition caused by eIF2 phosphorylation

RNA ◽  
2008 ◽  
Vol 14 (3) ◽  
pp. 593-602 ◽  
Author(s):  
V. V. Zeenko ◽  
C. Wang ◽  
M. Majumder ◽  
A. A. Komar ◽  
M. D. Snider ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
In Vitro Translation ◽  
Translation System ◽  
Translational Inhibition ◽  
Eif2 Phosphorylation

scholarly journals Heat shock causes a decrease in polysomes and the appearance of stress granules in trypanosomes independently of eIF2  phosphorylation at Thr169

2008 ◽  
Vol 121 (18) ◽  
pp. 3002-3014 ◽  
Author(s):  
S. Kramer ◽  
R. Queiroz ◽  
L. Ellis ◽  
H. Webb ◽  
J. D. Hoheisel ◽  
...  
Keyword(s):  
Heat Shock ◽  
Stress Granules ◽  
Eif2 Phosphorylation

scholarly journals Ribosome profiling uncovers selective mRNA translation associated with eIF2 phosphorylation in erythroid progenitors

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0193790 ◽  
Author(s):  
Nahuel A. Paolini ◽  
Kat S. Moore ◽  
Franca M. di Summa ◽  
Ivo F. A. C. Fokkema ◽  
Peter A. C. ‘t Hoen ◽  
...  
Keyword(s):  
Mrna Translation ◽  
Ribosome Profiling ◽  
Erythroid Progenitors ◽  
Eif2 Phosphorylation

scholarly journals Akt Determines Cell Fate Through Inhibition of the PERK-eIF2  Phosphorylation Pathway

2011 ◽  
Vol 4 (192) ◽  
pp. ra62-ra62 ◽  
Author(s):  
Z. Mounir ◽  
J. L. Krishnamoorthy ◽  
S. Wang ◽  
B. Papadopoulou ◽  
S. Campbell ◽  
...  
Keyword(s):  
Cell Fate ◽  
Eif2 Phosphorylation

Coping with stress: eIF2 kinases and translational control

2006 ◽  
Vol 34 (1) ◽  
pp. 7-11 ◽  
Author(s):  
R.C. Wek ◽  
H.-Y. Jiang ◽  
T.G. Anthony
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Protein Kinases ◽  
Translational Control ◽  
Environmental Stresses ◽  
Initiation Factor ◽  
Nutritional Deficiencies ◽  
Basic Leucine Zipper ◽  
Eif2α Kinase ◽  
Eif2 Phosphorylation

In response to environmental stresses, a family of protein kinases phosphorylate eIF2 (eukaryotic initiation factor 2) to alleviate cellular injury or alternatively induce apoptosis. Phosphorylation of eIF2 reduces global translation, allowing cells to conserve resources and to initiate a reconfiguration of gene expression to effectively manage stress conditions. Accompanying this general protein synthesis control, eIF2 phosphorylation induces translation of specific mRNAs, such as that encoding the bZIP (basic leucine zipper) transcriptional regulator ATF4 (activating transcription factor 4). ATF4 also enhances the expression of additional transcription factors, ATF3 and CHOP (CCAAT/enhancer-binding protein homologous protein)/GADD153 (growth arrest and DNA-damage-inducible protein), that assist in the regulation of genes involved in metabolism, the redox status of the cells and apoptosis. Reduced translation by eIF2 phosphorylation can also lead to activation of stress-related transcription factors, such as NF-κB (nuclear factor κB), by lowering the steady-state levels of short-lived regulatory proteins such as IκB (inhibitor of NF-κB). While many of the genes induced by eIF2 phosphorylation are shared between different environmental stresses, eIF2 kinases function in conjunction with other stress-response pathways, such as those regulated by mitogen-activated protein kinases, to elicit gene expression programmes that are tailored for the specific stress condition. Loss of eIF2 kinase pathways can have important health consequences. Mice devoid of the eIF2 kinase GCN2 [general control non-derepressible-2 or EIF2AK4 (eIF2α kinase 4)] show sensitivity to nutritional deficiencies and aberrant eating behaviours, and deletion of PEK [pancreatic eIF2α kinase or PERK (RNA-dependent protein kinase-like endoplasmic reticulum kinase) or EIF2AK3] leads to neonatal insulin-dependent diabetes, epiphyseal dysplasia and hepatic and renal complications.

scholarly journals Response of Three Different Viruses to Interferon Priming and Dithiothreitol Treatment of Avian Cells

2016 ◽  
Vol 90 (18) ◽  
pp. 8328-8340 ◽  
Author(s):  
Irene Lostalé-Seijo ◽  
José Martínez-Costas ◽  
Javier Benavente
Keyword(s):  
Protein Kinase ◽  
Vaccinia Virus ◽  
Vesicular Stomatitis Virus ◽  
Rna Binding ◽  
Initiation Factor ◽  
Type I ◽  
Avian Reovirus ◽  
Double Stranded Rna ◽  
Vesicular Stomatitis ◽  
Eif2 Phosphorylation

ABSTRACTWe have previously shown that the replication of avian reovirus (ARV) in chicken cells is much more resistant to interferon (IFN) than the replication of vesicular stomatitis virus (VSV) or vaccinia virus (VV). In this study, we have investigated the role that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) plays in the sensitivity of these three viruses toward the antiviral action of chicken interferon. Our data suggest that while interferon priming of avian cells blocks vaccinia virus replication by promoting PKR activation, the replication of vesicular stomatitis virus appears to be blocked at a pretranslational step. Our data further suggest that the replication of avian reovirus in chicken cells is quite resistant to interferon priming because this virus uses strategies to downregulate PKR activation and also because translation of avian reovirus mRNAs is more resistant to phosphorylation of the alpha subunit of initiation factor eIF2 than translation of their cellular counterparts. Our results further reveal that the avian reovirus protein sigmaA is able to prevent PKR activation and that this function is dependent on its double-stranded RNA-binding activity. Finally, this study demonstrates that vaccinia virus and avian reovirus, but not vesicular stomatitis virus, express/induce factors that counteract the ability of dithiothreitol to promote eIF2 phosphorylation. Our data demonstrate that each of the three different viruses used in this study elicits distinct responses to interferon and to dithiothreitol-induced eIF2 phosphorylation when infecting avian cells.IMPORTANCEType I interferons constitute the first barrier of defense against viral infections, and one of the best characterized antiviral strategies is mediated by the double-stranded RNA-activated protein kinase R (PKR). The results of this study revealed that IFN priming of avian cells has little effect on avian reovirus (ARV) replication but drastically diminishes the replication of vaccinia virus (VV) and vesicular stomatitis virus (VSV) by PKR-dependent and -independent mechanisms, respectively. Our data also demonstrate that the dsRNA-binding ability of ARV protein sigmaA plays a key role in the resistance of ARV toward IFN by preventing PKR activation. Our findings will contribute to improve the current understanding of the interaction of viruses with the host's innate immune system. Finally, it would be of interest to uncover the mechanisms that allow avian reovirus transcripts to be efficiently translated under conditions (moderate eIF2 phosphorylation) that block the synthesis of cellular proteins.

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