scholarly journals Hepatic Heme-Regulated Inhibitor (HRI) Eukaryotic Initiation Factor 2α Kinase: A Protagonist of Heme-Mediated Translational Control of CYP2B Enzymes and a Modulator of Basal Endoplasmic Reticulum Stress Tone

2010 ◽  
Vol 77 (4) ◽  
pp. 575-592 ◽  
Author(s):  
Poulomi Acharya ◽  
Jane-Jane Chen ◽  
Maria Almira Correia
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Translational Control ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Kinase A

scholarly journals Pancreatic eukaryotic initiation factor-2α kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress

2000 ◽  
Vol 346 (2) ◽  
pp. 281-293 ◽  
Author(s):  
Ruchira SOOD ◽  
Amy C. PORTER ◽  
Kun MA ◽  
Lawrence A. QUILLIAM ◽  
Ronald C. WEK
Keyword(s):  
Endoplasmic Reticulum ◽  
Drosophila Melanogaster ◽  
Caenorhabditis Elegans ◽  
Er Stress ◽  
Translational Control ◽  
Mammalian Cells ◽  
Transmembrane Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Α Subunit

In response to different cellular stresses, a family of protein kinases regulates translation by phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF-2α). Recently, we identified a new family member, pancreatic eIF-2α kinase (PEK) from rat pancreas. PEK, also referred to as RNA-dependent protein kinase (PKR)-like endoplasmic reticulum (ER) kinase (PERK) is a transmembrane protein implicated in translational control in response to stresses that impair protein folding in the ER. In this study, we identified and characterized PEK homologues from humans, Drosophila melanogaster and Caenorhabditis elegans. Expression of human PEK mRNA was found in over 50 different tissues examined, with highest levels in secretory tissues. In mammalian cells subjected to ER stress, we found that elevated eIF-2α phosphorylation was coincident with increased PEK autophosphorylation and eIF-2α kinase activity. Activation of PEK was abolished by deletion of PEK N-terminal sequences located in the ER lumen. To address the role of C. elegans PEK in translational control, we expressed this kinase in yeast and found that it inhibits growth by hyperphosphorylation of eIF-2α and inhibition of eIF-2B. Furthermore, we found that vaccinia virus K3L protein, an inhibitor of the eIF-2α kinase PKR involved in an anti-viral defence pathway, also reduced PEK activity. These results suggest that decreased translation initiation by PEK during ER stress may provide the cell with an opportunity to remedy the folding problem prior to introducing newly synthesized proteins into the secretory pathway.

scholarly journals Translational Control during Endoplasmic Reticulum Stress beyond Phosphorylation of the Translation Initiation Factor eIF2α

2014 ◽  
Vol 289 (18) ◽  
pp. 12593-12611 ◽  
Author(s):  
Bo-Jhih Guan ◽  
Dawid Krokowski ◽  
Mithu Majumder ◽  
Christine L. Schmotzer ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Translation Initiation ◽  
Translational Control ◽  
Translation Initiation Factor ◽  
Initiation Factor
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