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TorsinA was post-transcriptionally upregulated upon acute ER stress, suggesting a role in this response. Increased basal phosphorylation of eIF2alpha in DYT1 transgenic rats was associated with abnormal response to acute ER stress. Unbiased RNA-Seq-based transcriptomic analysis of embryonic brain tissue in heterozygous and homozygous DYT1 knockin mice confirmed presence of eIF2alpha dysregulation in the DYT1 brain.
Our study revealed that p-eIF2alpha was upregulated in breast cancer and represented a novel predictor of prognosis in patients with triple-negative subtype.
ABC50 N-terminal region interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2
hypusine-eIF5A-facilitated translation elongation promotes arsenite-induced polysome disassembly and stress granule assembly in cells subjected to adverse environmental conditions
analysis of the ER stress response in immunogenic cell death and the potential value of eIF2alpha phosphorylation as a biomarker for this clinically relevant variant of apoptosis [review]
The data highlight independent interactions of PP1 and eIF2alpha with GADD34, demonstrating that GADD34 functions as a scaffold both in vitro and in cells
These experiments connect embryonic stem cell growth factors to eIF2alpha phosphorylation.
We identified EIF2A phosphorylation as a novel early molecular event occurring in response to NAMPT inhibition and mediating protein synthesis arrest.
The results suggest that dephosphorylation of eIF2a by GADD34 plays an important role in doxorubicin resistance of MCF-7/ADR cells.
The Newcastle disease virus-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2a, which is mediated by continual activation of PKR and degradation of PP1.
GHRH and GHRH-R loops are involved in placental choriocarcinoma cell line viability and apoptosis through Akt and eIF2a pathways.
These findings suggest that phosphorylated-eIF2alpha regulates synaptic actions of nicotine in both mice and humans, and that reduced phosphorylated-eIF2alpha may enhance susceptibility to nicotine (and other drugs of abuse) during adolescence.
This review consolidates current information regarding eIF2alpha phosphorylation in neurons and its impact in neurodegenerative diseases.
Increased phosphorylation of eIF2alpha in chronic myeloid leukemia cells stimulates secretion of matrix modifying enzymes.
Stress-resistant translation of c-Src mRNA is mediated by eIF2A.
Results mechanistically link multiple forms of dystonia and put forth a new overall cellular mechanism for dystonia pathogenesis, impairment of eIF2alpha signaling, a pathway known for its roles in cellular stress responses and synaptic plasticity.
Single amino acid substitution in LC-CDR1 induces Russell body phenotype that attenuates cellular protein synthesis through eIF2alpha phosphorylation and thereby downregulates IgG secretion despite operational secretory pathway traffic.
These results demonstrate a previously unrecognized role of IL24 in inhibition of translation, mediated through both phosphorylation of eIF2alpha and dephosphorylation of 4E-BP1, and provide the first direct evidence for translation control of gene-specific expression by IL24
eukaryotic elongation factor 2 has a role in proliferation and invasion of lung squamous cell carcinoma
a novel, positive role for PKR activation and eIF2alpha phosphorylation in human globin mRNA splicing, is reported.
Caspase(s)-dependent proteolysis of molecular chaperones and eIF2alpha may be novel signaling pathways of apoptosis.
EIF2alpha regulates oligodendrocyte survival during differentiation.
We hypothesize that the essential role of methionine-charged initiator tRNA in forming ternary complex is responsible for the robust ability of methionine deficiency to induce ATF4 and the ISR even in the absence of GCN2 or eIF2alpha kinase activity.
ER stress-induced increase in ATF4 and CHOP expression is initiated by an increase in Atf4 and Chop mRNA, which is also dependent upon eIF2alpha phosphorylation.
Data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2alpha to emerge.
Endoplasmic reticulum stress suppressed CReP expression in an IRE1 alpha-dependent manner, which increased eIF2alpha phosphorylation and consequently attenuated protein synthesis.
eIF2alphaP acts as a molecular switch that dictates either cell survival or death by activated Akt in response to oxidative stress.
aberrant phosphorylation of eukaryotic initiation factor-2a (eIF2a) may induce synaptic failure and neurodegeneration through persistent translational inhibition of global protein synthesis.
Alteration of protein homeostasis and eIF2alpha phosphorylation status by pathogenic huntingtin appears to be an important cause of striatal cell death.
Data indicate that prolonged endoplasmic reticulum stress inhibits protein synthesis independently of translation initiation factor eIF2alpha-P.
This study demonistrated that Genetic deletion of eIF2alpha kinase PERK prevented enhanced phosphorylation of eIF2alpha and deficits in protein synthesis, synaptic plasticity and spatial memory in animal disease model of Alzheimer's disease.
eIF2alpha phosphorylation in the context of the ER stress response plays a role in cell survival by counteracting the p53-mediated mitochondrial apoptosis in response to statins.
eIF2a is hyperphosphorylated in the cortex of aged mice. Young human-ApoE4 targeted-replacement mice show increased p-eIF2a/eIF2a levels in both cortex and hippocampus.
the induction of REDD1 gene expression was shown to require the protein kinase PERK and enhanced phosphorylation of its substrate, the alpha-subunit of eukaryotic initiation factor 2.
Data show that protein kinase R as the principal kinase that mediates eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation by large RasGAP SH3-binding protein (G3BP)-induced granules.
PTP1B deficiency modulates PERK-eIF2alpha phosphorylation and protein synthesis
Ectopic expression of CReP restored the sensitivity of the Pten mutant hepatocytes to oxidative stress, confirming the functional significance of the downregulated CReP and upregulated phospho-eIF2alpha
It was shown that urea-inducible GCN2 activation initiates the phosphorylation of eIF2alpha and the downstream increase of activating transcription factor 3.
regulation of translation through eIF2alpha phosphorylation is dispensable in hematopoietic reconstitution but essential during late B-cell development.
eIF2alpha phosphorylation acts in a cytoprotective manner, i.e., prevents apoptosis.
In conclusion, the immediate-early IE180 protein of pseudorabies virus has the previously uncharacterized ability to suppress phosphorylation levels of the eukaryotic translation initiation factor eIF2alpha.
Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models.
The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2\; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3\; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987
, eukaryotic translation initiation factor 2 subunit 1
, eukaryotic translation initiation factor 2 subunit alpha
, eukaryotic translation initiation factor 2, subunit 1 alpha
, eukaryotic translation initiation factor 2, subunit 1 alpha, like
, eukaryotic translation initiation factor 2A
, eukaryotic translation initiation factor 2 alpha subunit
, Eukaryotic translation initiation factor 2 subunit 1
, eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa
, eukaryotic translation initiation factor 2, subunit 1 (alpha )
, eukaryotic initiation factor 2alpha
, eukaryotic translation initiation factor 2
, eukaryotic translation initiation factor 2alpha
, minute (1) 14C