Kinases protein eukaryotic initiation factor 2. Medical search. Frequent questions

For instance, it can be activated by oncogenic mutations of PTEN, VHL, the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. (spandidos-publications.com)
The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. (hindawi.com)
Further mechanistic studies revealed that these functions were controlled by the eukaryotic initiation factor (eIF) 4E and the mitogen-activated protein kinase (MAPK) interacting protein kinase (MNK) signaling pathways, which regulate which mRNAs will be translated. (lu.se)

This inhibits further cellular mRNA translation, thereby preventing viral protein synthesis. (wikipedia.org)
Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)
According to the metabotropic glutamate receptor (mGluR) theory of FXS, excessive protein synthesis downstream of mGluR5 activation causes the synaptic pathophysiology that underlies multiple aspects of FXS. (jneurosci.org)
Here, we use an in vitro assay of protein synthesis in the hippocampus of male Fmr1 knock-out (KO) mice to explore the molecular mechanisms involved in this core biochemical phenotype under conditions where aberrant synaptic physiology has been observed. (jneurosci.org)
We find that elevated basal protein synthesis in Fmr1 KO mice is selectively reduced to wild-type levels by acute inhibition of mGluR5 or ERK1/2, but not by inhibition of mTOR (mammalian target of rapamycin). (jneurosci.org)
These results suggest that the ERK1/2 pathway, and other neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent additional therapeutic targets for FXS. (jneurosci.org)
Although it is now clear that mGluR5 participates in the pathogenesis of FXS, at least in animal models, it is still poorly understood how Gp1 mGluRs trigger protein synthesis and how this process is altered in the absence of FMRP to disrupt synaptic function. (jneurosci.org)
One source of confusion may be that proxy measures of protein synthesis, such as mGluR-LTD or phosphorylation of signaling molecules, have been used in intact hippocampal slice preparations, whereas metabolic labeling experiments have been performed in synaptoneurosome preparations of cortex that are not easily related to altered hippocampal synaptic plasticity. (jneurosci.org)
A strong rationale for taking this approach is that slice has been shown to accurately reproduce the in vivo phenotype of elevated basal protein synthesis in the Fmr1 KO hippocampus (cf. (jneurosci.org)
Our data suggest that elevated protein synthesis in the Fmr1 KO is due to saturation of mRNA translation downstream of the MAP kinase ERK1/2 which is basally activated by mGluR5. (jneurosci.org)
The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. (scienceopen.com)
In human cells infected with herpes simplex virus 1 the double-stranded RNA-dependent protein kinase (PKR) is activated but phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff of protein synthesis is observed only in cells infected with gamma(1)z34.5- mutants. (scienceopen.com)
These results indicate that in infected cells, gamma(1)34.5 interacts with and redirects phosphatase to dephosphorylate eIF-2alpha to enable continued protein synthesis despite the presence of activated PKR. (scienceopen.com)
The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date. (scienceopen.com)
Endoplasmic reticulum stress (ERS) is a state induced by increased synthesis of intracellular proteins, accumulation of mal-folded proteins, changes in cytosolic calcium levels, or imbalances in endoplasmic reticulum (ER) redox homeostasis [ 8 ]. (biomedcentral.com)
Akt pathways have effects on apoptosis, protein synthesis, metabolism and cell cycle. (springer.com)
AMPK pathways inhibit biosynthetic pathways with energy consumption, such as protein, fatty acid and glycogen synthesis. (springer.com)
The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis. (bvsalud.org)
In many cell lines, exposure to rapamycin results in a relatively small decrease in overall protein synthesis (~15-20%), but dose result specifically in G1 cell cycle arrest. (biomedcentral.com)
The preferential replication of reovirus in cells with activated RAS is due to RAS's ability to inhibit double-stranded RNA-activated protein kinase (PKR), a key sensor that recognizes viral particles and results in abrogation of protein synthesis by phosphorylation of eukaryotic initiation factor 2 alpha (eif2α) [ 7 ]. (biomedcentral.com)
Addition of heme in vitro stimulates cell-free protein synthesis strikingly. (iisc.ac.in)
Chloroquine inhibits the heme-dependent protein synthesis in the parasite lysate. (iisc.ac.in)
The drug has also been found to inhibit parasite protein synthesis in situ at therapeutic concentrations soon after addition to parasite cultures. (iisc.ac.in)
Ribosomes as well as the S-100 fraction isolated from such chloroquine-treated cultures are defective in protein synthesis. (iisc.ac.in)
Addition of hemin plus glucose 6-phosphate or high concentrations of GTP, cAMP, and an active preparation of eIF-2 to the parasite cell-free system restores protein synthesis to a significant extent in chloroquine-treated cultures. (iisc.ac.in)
Under conditions of inhibition of protein synthesis in situ by chloroquine in the culture, the parasite eukaryotic initiation factor 2-alpha- (eIF-2-alpha) is phosphorylated in the parasite lysate to a greater extent than that observed in the control culture. (iisc.ac.in)
It is proposed that chloroquine inhibits heme-dependent protein synthesis in the parasite and this is an early event mediating the growth-inhibitory effects of the drug. (iisc.ac.in)
Malaria Parasite;Cell-Free System;Translation;Protein Synthesis Insitu;Eukaryotic Initiation Factor-2-Alpha Kinase. (iisc.ac.in)
A mechanism for the control of protein synthesis by adenovirus VA RNAI. (wikidata.org)
The UPR activation involves three major downstream effects including reduction in protein synthesis to reduce ER load, enhancement of ER protein folding capacity and upregulation of ER-associated protein degradation (ERAD). (distantreader.org)
It also stimulates glycogen synthesis by inhibiting glycogen synthase kinase 3 (GSK3) and activating glycogen synthase. (alliedacademies.org)
When activated, AMPK phosphorylates and inhibits enzymes involved in ATP-consuming processes, such as fatty acid synthesis (e.g., acetyl-CoA carboxylase, ACC) and protein synthesis (e.g., mammalian target of rapamycin, mTOR). (alliedacademies.org)
Activation of EIF2AK2 leads to its autophosphorylation and then phosphorylation of its natural substrate, the alpha subunit of eukaryotic protein synthesis initiation factor-2. (signalchem.com)
Obese and diabetic topics have raised plasma degrees of nonesterified essential fatty acids (NEFAs) and hyperglycemia, that are believed to trigger reduced insulin synthesis and impaired blood sugar responsiveness in pancreatic -cells, termed glucolipotoxicity [2] also, [3]. (cgp60474.com)
They both exert regulatory control by shutting down protein synthesis, turning on genes, and degrading transcripts. (ucsb.edu)
Activation of PERK elicits a transient global protein synthesis shutdown through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). (ucsb.edu)
Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97. (ox.ac.uk)
VCP inhibition had an impact on two key regulators of protein synthesis, eukaryotic initiation factor 2α (eIF2α) and mechanistic target of rapamycin complex 1 (mTORC1), and attenuated global protein synthesis. (ox.ac.uk)
Thus, cancer cell death following VCP inhibition was linked to inadequate fine-tuning of protein synthesis and activity of PPP1R15A/PP1c. (ox.ac.uk)
Thus, depletion of VCP enzymatic activity triggers cancer cell death in part through inadequate regulation of protein synthesis and amino acid metabolism. (ox.ac.uk)
However, the G1-specific synthesis of factors required for DNA replication was not reduced by ultraviolet radiation. (ox.ac.uk)

GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. (hindawi.com)
Neuronal nitric oxide synthase (nNOS) and vitamin D receptor (VDR) expression were measured, as well as ER stress markers, including glucose-regulated protein78 (GRP78), protein kinase-like endoplasmic reticulum kinase (PERK) phosphorylation, eukaryotic initiation factor 2 alpha(eIF-2 alpha) phosphorylation, and CCAAT enhancer-binding protein homologous protein (CHOP). (cheric.org)
Finally, DDR/UPR interplay activated a pro-survival autophagy via PERK/eIF2alpha axis in MM and IRE1alpha/JNK axis in PEL cells, since in the latter case PERK/eIF2alpha activation could be prevented by KSHV that, as other herpesviruses, tries to avoid the blocks of protein translation that this pathway may induce. (uniroma1.it)
4 Upon dissociation from GRP78, the transmembrane kinase PERK is activated by oligomerisation and autophosphorylation. (distantreader.org)
1. Baltzis, D. et al: The eIF2alpha kinases PERK and PKR activate glycogen synthase kinase 3 to promote the proteasomal degradation of p53. (signalchem.com)
In the UPR, the sensor proteins are the kinase PERK and the kinase/endoribonuclease IRE1 work together to recognize and respond to unfolded proteins. (ucsb.edu)
Sensors and effectors are coupled as specific domains of single proteins in PERK, PKR and IRE1. (ucsb.edu)

Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
The protein levels of phospho-phosphatidylinositol 3-kinase, protein kinase B, phospho-eukaryotic initiation factor 4E binding protein-1 (p-4E-BP1), 4E-BP1 and ribosomal protein S6 kinase 1, in the liver of fish fed the 0.84% diet were higher than those in fish fed the 0.40% diet. (researchsquare.com)
Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. (uleth.ca)

Once active, PKR is able to phosphorylate the eukaryotic translation initiation factor eIF2α. (wikipedia.org)
The EIF2AK4 protein can turn on (activate) another protein called eIF2 alpha (eIF2α), which helps control protein production. (medlineplus.gov)
When cells are under stress, for example when the level of protein building blocks (amino acids) is too low, EIF2AK4 activates eIF2α. (medlineplus.gov)
When turned on, eIF2α stimulates processes that reduce protein production, which helps conserve amino acids. (medlineplus.gov)
In addition, activated eIF2α can trigger production of certain proteins called transcription factors, which control gene activity. (medlineplus.gov)
The transcription factors regulated by eIF2α control the activity of genes involved in processes that help reduce the stress on the cell. (medlineplus.gov)
LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2α kinase general control nonderepressible 2 (GCN2). (jci.org)
In most metazoans, GCN2 is one of the four known kinases that phosphorylate eukaryotic initiation factor 2, α subunit (eIF2α) to inhibit translation initiation [ 19 ]. (biomedcentral.com)
We identified an elevated integrated stress response (ISR) characterized by phosphorylation of eIF2α as a relevant molecular mechanism which is able to affect translation of myelin proteins. (biomedcentral.com)
Activated Benefit phosphorylates and inhibits eukaryotic initiation aspect 2 (eIF2) resulting in global translational attenuation. (cgp60474.com)
Some of the proteotoxic effects of VCP depletion depended on the eIF2α phosphatase, protein phosphatase 1 regulatory subunit 15A (PPP1R15A)/PP1c, but not on mTORC1, although there appeared to be cross-talk between them. (ox.ac.uk)

In response to amino acid deprivation or UV irradiation, GCN2 phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2a) at Ser51 and induces a delay in entry to S phase of the cell cycle. (rndsystems.com)
and (iii) the alpha subunit in purified eIF-2 phosphorylated in vitro is specifically dephosphorylated by S10 fractions of wild-type infected cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2alpha-P phosphatase activity of gamma(1)34.5- virus infected cells is lower than that of mock-infected cells. (scienceopen.com)
Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. (scienceopen.com)

PKR also has pro-inflammatory functions, as it can mediate the activation of the transcription factor NF-kB, by phosphorylating its inhibitory subunit, IkB. (wikipedia.org)

The mGluR5-ERK1/2 pathway is not constitutively overactive in the Fmr1 KO, however, suggesting that mRNA translation is hypersensitive to basal ERK1/2 activation in the absence of FMRP. (jneurosci.org)
We find that hypersensitivity to ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility in the Fmr1 KO. (jneurosci.org)
Using Ingenuity Pathway Analysis bioinformatics software, it was revealed that the activity of multiple signaling pathways varied alongside the changes in expression of these proteins, and c‑SRC was identified as a protein involved in a number of these signaling pathways, with its activity varying markedly upon the acquisition of resistance. (spandidos-publications.com)
The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. (biomedcentral.com)
Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2 -dependent manner. (biomedcentral.com)
IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. (biomedcentral.com)
EIF4EBP2 mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase pathway. (prospecbio.com)
Features of signaling through the mammalian target of rapamycin complex 1 pathway via the tuberous sclerosis 1/tuberous sclerosis 2 complex. (medlink.com)
Von Roretz, C & Gallouzi, IE 2010, ' Protein kinase RNA/FADD/caspase-8 pathway mediates the proapoptotic activity of the RNA-binding protein human antigen R (HuR) ', Journal of Biological Chemistry , vol. 285, no. 22, pp. 16806-16813. (edu.sa)
Phosphatidylinositol-3-kinase (PI3-K) pathway has been reported as an important intracellular mediator frequently activated in cancer cells [ 2 ]. (biomedcentral.com)
Insulin signaling pathway activates phosphatidylinositol 3-kinase (PI3K), which phosphorylates and activates Akt (also known as protein kinase B). Akt regulates glucose transport by promoting the translocation of glucose transporters, such as GLUT4, to the plasma membrane. (alliedacademies.org)
ER stress cross-talks to the mitochondrial or intrinsic death pathway via p53-upregulated modulator of apoptosis (Puma) and JNK-dependent upregulation of the Death protein (DP5) [27]. (cgp60474.com)

Possible mechanisms for developing acquired resistance to anti-cancer drugs include mutations of genes encoding proteins that are the targets of drugs or are present in downstream pathways of proteins inhibited by drugs as well as the activation of collateral pathways ( 19 , 20 ). (spandidos-publications.com)
DR acts by promoting stress response pathways and preventing age-related functional decline, delaying the appearance of cardiovascular diseases, type 2 diabetes, and neurodegeneration in mammals, including non-human primates [ 6 ]. (biomedcentral.com)
p97) is an essential regulator of protein degradation in multiple pathways and has emerged as a target for cancer therapy. (ox.ac.uk)

Identification of a 90-kDa polypeptide which associates with adenovirus VA RNAI and is phosphorylated by the double-stranded RNA-dependent protein kinase. (wikidata.org)
Reduced activity of the interferon-induced double-stranded RNA-dependent protein kinase during a heat shock stress. (wikidata.org)

Lenvatinib is an oral multi-kinase inhibitor that inhibits mainly vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptor (PDGFR) α, c-KIT, and RET ( 11 ). (spandidos-publications.com)
As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. (biomedcentral.com)
Even though EIF4EBP2 protein binds eIF4E and inhibits translation initiation, growth factors can release this inhibition by a phosphorylation-dependent disruption. (prospecbio.com)

Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. (inra.fr)

Donnelly N, Gorman AM, Gupta S, Samali A. The eIF2alpha kinases: their structures and functions. (medlineplus.gov)
The cell cycle delay was totally dependent on the Gcn2 kinase, a sensor of the nutritional status, and was accompanied by phosphorylation of the translation initiation factor eIF2alpha and by a general depression of translation. (ox.ac.uk)

PKR also activates several mitogen-activated protein kinases (MAPK) to lead to inflammation. (wikipedia.org)

Treating SMMC-7721 cells with 5-Fu leads to apoptosis of the cells, and reduction in telomerase activity, as well as a dramatic reduction in the activated form of p70 S6 kinase, a mTOR substrate. (biomedcentral.com)
Treating SMMC-7721 cells with Rapamycin, a specific mTOR inhibitor, significantly reduce hTERT protein level but did not affect hTERT transcription. (biomedcentral.com)
Phosphorylation by mTOR of 4E-BP1 disrupts its binding to eIF4E, a protein that binds the 5'-cap structure of mRNA. (biomedcentral.com)

Protein kinase RNA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is an enzyme that in humans is encoded by the EIF2AK2 gene on chromosome 2. (wikipedia.org)
GCN2, also known as EIF2AK4, is a widely expressed 190 kDa ribosome-associated Ser/Thr kinase that plays an important role in the control of protein translation. (rndsystems.com)
Fragile X syndrome (FXS) is caused by loss of the FMR1 gene product FMRP (fragile X mental retardation protein), a repressor of mRNA translation. (jneurosci.org)
Predicted to enable eukaryotic translation initiation factor 2alpha kinase activity. (zfin.org)
Orthologous to human EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3). (zfin.org)
EIF4EBP2 belongs to the eukaryotic translation initiation factor 4E binding protein family. (prospecbio.com)
This effect, however, does not require the phosphorylation of the eukaryotic translation initiation factor 2α. (edu.sa)
17 and 14 genes encode BR serine/threonine-protein kinase 2 (BRSK2) and eukaryotic translation-initiation factor 2-alpha kinase 3 (Eif2ak3), respectively. (onacademic.com)
This event leads to the paradoxical translation of a few select mRNAs that contain regulatory upstream open reading frames (uORFs), such as the mRNAs encoding the transcription factors ATF4 and CHOP. (ucsb.edu)
However, a block on protein translation that was itself cytotoxic alleviated stress signaling and reduced cell death triggered by VCP inhibition. (ox.ac.uk)
VCP inhibitors also perturbed intracellular amino acid levels, activated eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4), and enhanced cellular dependence on amino acid supplies, consistent with a failure of amino acid homeostasis. (ox.ac.uk)
In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2αand attenuates viral protein translation. (uleth.ca)

This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
5′-GACGTG-3′) on the promoter region in various target genes ( 1 , 2 ). (spandidos-publications.com)
Cox regression analysis identifies independent prognostic factors for these patients, and enrichment analysis of prognosis-related genes was also performed. (biomedcentral.com)
The cell division cycle of the unicellular eukaryote Trypanosome brucei is tightly regulated despite the paucity of transcriptional control that results from the arrangement of genes in polycistronic units and lack of dynamically regulated transcription factors. (lancs.ac.uk)
Compared with 0.40% dietary methionine, 1.28% methionine enhanced the mRNA levels of the hepatic gluconeogenesis related genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, and the muscular glycolysis related genes phosphofructokinase (PFK) and pyruvate kinase (PK). (researchsquare.com)
This spliced form of XBP1 then translates into a transcription factor, which further translocates into the nucleus where it induces expression of a wide variety of genes including ER-associated chaperones and protein folding enzymes to increase ER size and folding capacity. (distantreader.org)
Activated ATF6 mediates transcription of genes encoding ER chaperone proteins also. (cgp60474.com)
Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). (inra.fr)

Previous studies reported that ATF-3 was induced by treating cells with antitumorigenic compounds [ 14 - 18 ] and a phosphoinositide 3-kinase inhibitor [ 19 ]. (hindawi.com)
The eIF-2alpha-P phosphatase activities are sensitive to inhibitor 2. (scienceopen.com)
Lenvatinib, a multi‑kinase inhibitor, serves a crucial role in the treatment of unresectable hepatocellular carcinoma (HCC). (spandidos-publications.com)
In terms of the disease control rate (complete response + partial response + stable disease ratio), response rate (complete response + partial response ratio), median progression-free survival, and median time to progression, lenvatinib shows significantly better results compared with sorafenib, another oral multi-kinase inhibitor (75.5 vs. 60.5%, 24.1 vs. 9.2%, 7.4 vs. 3.7 months, 8.9 vs. 3.7 months, respectively) ( 7 ). (spandidos-publications.com)

Murguia JR, Serrano R. New functions of protein kinase Gcn2 in yeast and mammals. (medlineplus.gov)
GCN2 contains an RWD domain (aa 21-134), a pseudo-kinase domain (aa 296-539), a catalytic domain (aa 590-1001), and a histidyl tRNA synthase-like domain (aa 1022-1493) followed by a C-terminal ribosome interacting region. (rndsystems.com)
GCN2 is an evolutionarily conserved serine/threonine kinase that senses amino acid restriction through binding to uncharged tRNAs [ 18 ]. (biomedcentral.com)

and high protein levels of stomatin-like protein 2 and epidermal growth factor receptor ( 17 , 18 ). (spandidos-publications.com)
PTPRC/CD45: Protein Tyrosine Phosphatase Receptor Type C, CD45 antigen. (ox.ac.uk)
However, if the stress on the ER is chronic or severe and quality control of protein folding cannot be met, ER activates its stress receptor, the unfolded protein response, which triggers programmed cell death [ 9 ]. (biomedcentral.com)
Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)

Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. (hindawi.com)
abstract = "The RNA-binding protein human antigen R (HuR) has been implicated in apoptosis in multiple ways. (edu.sa)
2. Alirezaei, M. et al: Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons. (signalchem.com)
Long term and extreme ER tension induced -cell apoptosis is certainly connected with c-jun N-terminal kinase (JNK) activation [9], [15]. (cgp60474.com)

In situations of viral infection, the dsRNA created by viral replication and gene expression binds to the N-terminal domain, activating the protein. (wikipedia.org)
The EIF2AK4 gene provides instructions for making a protein that helps direct a cell's response to changes that could damage the cell. (medlineplus.gov)
The EIF2AK4 gene mutations involved in PVOD likely lead to a complete loss of functional protein. (medlineplus.gov)
The carboxyl-terminal 64 aa of gamma(1)34.5 protein are homologous to the corresponding domain of MyD116, the murine growth arrest and DNA damage gene 34 (GADD34) protein and the two domains are functionally interchangeable in infected cells. (scienceopen.com)
The use of a muscle creatine kinase germline knockout of the gene encoding Ire1/Ern1 shifts the focus from traditional studies of tissue repair toward the regenerating myofibers. (elifesciences.org)
Following 25 cycles of treatment over 23 months, a second biopsy was collected and immunohistochemical analyses revealed the presence of reovirus replication and induction of the ER stress-related gene GRP78/BIP and the pro-apoptotic protein NOXA. (biomedcentral.com)
Comprehensive gene expression programs are subsequently initiated, allowing the cell to either resolve the protein folding stress or die trying. (ucsb.edu)

GRP78 has a high affinity for misfolded and unfolded proteins: when luminal load of misfolded protein increases, GRP78 is released from the ER stress sensors, which are then free to initiate downstream signalling outside the ER. (distantreader.org)
The dissociation of GRP78 allows IRE1 dimerisation and activation of C-terminal endoribonuclease activity, which non-canonically splices a 26-base pair intron from the X-box binding protein 1 (XBP1) mRNA to produce the spliced form of XBP1 (sXBP1). (distantreader.org)

In contrast to eIF-2alpha-P phosphatase activity, extracts of mock-infected cells exhibit a 2-fold higher phosphatase activity on [32P]phosphorylase than extracts of infected cells. (scienceopen.com)

Deviations from homeostasis are quickly and effectively identified by specialized sensor proteins that relay information to downstream effectors, which initiate appropriate actions to restore homeostasis. (ucsb.edu)

A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. (bvsalud.org)
The double stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. (wikidata.org)

PKR is a serine/tyrosine kinase that is 551 amino acids long. (wikipedia.org)

In addition, muscular PEPCK and glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% methionine. (researchsquare.com)

PKR also participates in the mitochondrial unfolded protein response (UPRmt). (wikipedia.org)
Using a wide range of biochemical and lipidomic analyses, we demonstrated that ABTL0812 increases cellular long-chain dihydroceramides by impairing DEGS1 (delta 4-desaturase, sphingolipid 1) activity, which resulted in sustained ER stress and activated unfolded protein response (UPR) via ATF4-DDIT3-TRIB3 that ultimately promotes cytotoxic autophagy in cancer cells. (nih.gov)
UPR: unfolded protein response. (nih.gov)
We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). (nature.com)
The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. (elifesciences.org)
Hasnain, Sumaira Z title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection date: 2018-04-03 journal: Clin Transl Immunology DOI: 10.1002/cti2.1014 sha: 6a80b22e84d2692545c6f11d7cb4c96602a25c39 doc_id: 3122 cord_uid: 07dlf3zw Protein folding in the endoplasmic reticulum (ER) is subject to stringent quality control. (distantreader.org)
When protein secretion demand exceeds the protein folding capacity of the ER, the unfolded protein response (UPR) is triggered as a consequence of ER stress. (distantreader.org)
As a result, the ER has evolved a regulatory network, known as the unfolded protein response (UPR), to control the protein folding process. (distantreader.org)
The Unfolded Protein Response (UPR) , the stress response network of the endoplasmic reticulum (ER), exquisitely illustrates this concept. (ucsb.edu)

AMP-Activated Protein Kinase (AMPK) is a master regulator of cellular energy status. (alliedacademies.org)

1 Protein Kinases and Signal Transduction Laboratory, Departament De Bioquímica I Biologia Molecular and Institut De Neurociències, Universitat Autònoma De Barcelona (UAB), Barcelona, Spain. (nih.gov)

ATF4 activates the transcription of C/EBP homologous proteins (CHOP), considered to mediate palmitate-induced -cell loss of life [10], [11]. (cgp60474.com)

Protein kinase-R is activated by double-stranded RNA (dsRNA), introduced to the cells by a viral infection. (wikipedia.org)
Binding to dsRNA is believed to activate PKR by inducing dimerization of the kinase domains and subsequent auto-phosphorylation reactions. (wikipedia.org)
In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. (bvsalud.org)

Human HTT codes for a large protein of 3144 amino acids, which is ubiquitously expressed in various tissues and is present in several sub-cellular locations. (nature.com)
Using EBNA3C amino acids 365-545 in a yeast two hybrid screen, we found an interaction with the Growth Arrest and DNA-damage protein, Gadd34. (scienceopen.com)
Methionine is an essential amino acid, that affects the metabolism of protein, lipid and glucose. (researchsquare.com)

Many of the observed effects of VCP inhibition differed from the effects triggered by proteasome inhibition or by protein misfolding. (ox.ac.uk)

Endoplasmic reticulum stress (ERS) is a self-protective mechanism resulting from an imbalance in quality control of unfolded proteins when cells are stressed, which plays an active role in lung cancer development, but the relationship between ERS and the pathological characteristics and clinical prognosis of LUAD patients remains unclear. (biomedcentral.com)

They modulate energy metabolism through the deacetylation of various substrates, including transcription factors, metabolic enzymes, and histones. (alliedacademies.org)

Under normoxic conditions, prolyl hydroxylases (PHDs) hydroxylate the cite-specific proline residues of HIF-1α in a reaction that uses O 2 as a substrate. (spandidos-publications.com)
EIF2AK2 acts as a critical mediator of gp120 neurotoxicity and is a substrate for a family of protein kinases that respond to various forms of environmental stress. (signalchem.com)

Dynamic IRE1 splices X-box binding proteins-1 (Xbp)-1 mRNA, translating into a dynamic transcription aspect sXbp-1 that induces ER chaperones and ER-associated proteins degradation. (cgp60474.com)
The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. (ox.ac.uk)

The success of the approach developed was critically dependent on protein extraction yield and purification quality, and the reproducibility of gel electrophoresis and nanoHPLC separations. (speciation.net)
Here, we show that this cleavage event is dependent on protein kinase RNA (PKR). (edu.sa)

Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen and vital to many aspects of cancer biology. (spandidos-publications.com)
Sestrin2, a stress-inducible protein, is primarily involved in cellular responses to various stresses. (bvsalud.org)
Aggregated misfolded proteins in the ER cause cellular stress, which if unresolved can lead to cell death. (distantreader.org)

ER stress caused by excess of unfolded proteins leads to inflammatory responses. (wikipedia.org)
Previous studies have revealed that endoplasmic reticulum (ER) stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER, contributing to degenerative musculoskeletal diseases. (bvsalud.org)
The accumulation of reoviral protein was associated with ER stress induction and caspase-3 processing suggesting that Reolysin and gemcitabine treatment exhibited direct pro-apoptotic activity against the tumor. (biomedcentral.com)
How do cells sense, respond, and adapt to protein-folding stress or harmful RNAs? (ucsb.edu)
In the UPR, stress sensors recognize unfolded proteins in the ER lumen and relay this information to the nucleus. (ucsb.edu)

Here, PKR is induced via the transcription factor AP-1 and activated independently of PACT. (wikipedia.org)
The genetic model of DR - the eat-2 mutant - has a decreased pumping rate, thus ingesting less bacteria, and requires the FoxA transcription factor PHA-4 [ 8 ] and the dimethoxy ubiquinone hydroxylase CLK-1 [ 9 ] to extend its lifespan. (biomedcentral.com)
On the other hand, activation of IRE1 results in the production of the transcription factor XBP1 through a well-understood unconventional splicing mechanism. (ucsb.edu)

eukaryotic translational initiation aspect-2 kinase 3 (Benefit), inositol-requiring enzyme 1 (IRE1) and activating transcription aspect 6 (ATF6) thus activating these protein. (cgp60474.com)

Detection of elevated ER tension marker appearance including ATF3, Bip and CHOP in mouse islets subjected to raised lipids and high blood sugar and in -cells of type 2 diabetics supports the participation of ER tension in the pathogenesis of Type 2 diabetes [12]C[14]. (cgp60474.com)

Among these transcription factors, hypoxia-inducible factor-1 (HIF-1) is one of the most important factors that play a critical role in controlling oxygen delivery and metabolic adaptation to hypoxic conditions. (spandidos-publications.com)

Anatomy21

Organisms17

Diseases1

Chemicals and Drugs141

Analytical, Diagnostic and Therapeutic Techniques and Equipment19

Phenomena and Processes56

Disciplines and Occupations1

Technology, Industry, Agriculture1

Information Science3

Mitogen-activa3

Synthesis41

PERK7

Ribosomal3

EIF211

Alpha subunit3

Subunit1

Pathway12

Pathways3

Double-stranded RNA-dependent prote2

Inhibits3

Phosphorylation of eukaryotic1

EIF2alpha2

MAPK1

MTOR3

Translation12

Genes8

Inhibitor4

Gcn23

Receptor4

Apoptosis4

Gene7

GRP782

2alpha1

Downstream1

Induced by interferon2

Tyrosine kinase1

Glycogen1

Unfolded protein9

AMPK1

Signal Transduction1

Activates1

DsRNA3

Amino3

Inhibition1

Endoplasmic reticulum stress1

Enzymes1

Substrate2

Degradation2

Dependent2

Cellular3

Stress5

Transcription factor3

Ire11

CHOP1

Inducible1