Global protein synthesis translation initiation eukaryotic initiation factor 2. Medical search. Frequent questions

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the EIF2AK3 gene. (wikipedia.org)
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)
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)
Three arms exist in the ER stress response: the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1) pathways, where each of the sensor proteins is a membrane protein ( Figure 1 ). (encyclopedia.pub)
The mammalian ER stress response consists of three arms: the inositol-requiring enzyme 1 (IRE1), protein kinase R (PKR)-like ER kinase (PERK), and activating transcription factor 6 (ATF6) pathways. (encyclopedia.pub)
b) 4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (biomedcentral.com)
Recent evidence links synaptic plasticity and mRNA translation, via the eukaryotic elongation factor 2 kinase (eEF2K) and its only known substrate, eEF2. (nature.com)
eEF2 is itself regulated by inhibitory phosphorylation at Thr56 by an upstream kinase, eEF2 kinase (eEF2K), also known as calmodulin-dependent protein kinase III. (nature.com)
eIF-2-alpha kinase GCN2;Eukaryotic translation initiation factor 2-alpha kinase 4;GCN2;GCN2 eIF2alpha kinase;GCN2-like protein;general control nonderepressible 2;PVOD2. (avivasysbio.com)
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability (PubMed:25329545). (avivasysbio.com)
Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). (avivasysbio.com)
The pathways that control protein translation were investigated by immunoblotting explant lysates for PKR, PERK (PKR like endoplasmic reticulum kinase), eIF2a (eukaryotic initiation factor 2a), eEFs (eukaryotic elongation factors), and AMP-dependent kinase. (ox.ac.uk)
Explants were also loaded in the presence of inhibitors of PKR, the fibroblast growth factor (FGF) receptor and PI3 kinase. (ox.ac.uk)
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)
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)
Under normal conditions, BiP binds to the lumenal domains of Ire1α, Ire1β and PERK (Eukaryotic translation initiation factor 2-alpha kinase 3), and prevents their homodimerization transport to the Golgi apparatus. (russnewton.com)
Background The serine-threonine protein kinase mammalian target of rapamycin (mTOR), which is definitely inhibited from the immunosuppressant drug rapamycin regulates several intracellular pathways in response to numerous extracellular signals, nutrient availability, energy status of the cell and stress. (researchensemble.com)
These pathways involve mTOR-dependent activation of the 70 kDa ribosomal protein S6 kinase (p70S6K) as well as the inactivation of the repressor of mRNA translation, eukaryotic initiation element 4E (eIF4E) binding protein (4EBP) [1,2]. (researchensemble.com)
EIF2AK2 (also known as double-stranded RNA-activated protein kinase) is a protein kinase that has been shown to be involved in HIV/gp120-associated neurodegeneration (1). (signalchem.com)
2. Alirezaei, M. et al: Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons. (signalchem.com)

The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. (wikipedia.org)
The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event-the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). (ucsf.edu)
Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global protein synthesis via the inhibitory effects of eIF2α-P on eIF2B, the guanine exchange factor (GEF) for eIF2. (ucsf.edu)
ISRIB analogues make cells insensitive to the effects of eIF2α-P by activating the GEF activity of eIF2B and allowing global protein synthesis to proceed with residual unphosphorylated eIF2α. (ucsf.edu)
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)
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)
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)
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)
Phosphorylation of eIF2α on Ser51 inhibits 5' cap-dependent mRNA translation, resulting in the global suppression of protein synthesis to facilitate adaptation to a variety of stresses linked to protein synthesis, including proteotoxic stress, viral replication, heme depletion and amino acid withdrawal [ 2 ]. (biomedcentral.com)
Paradoxically, eIF2α phosphorylation also results in the increased translation of select mRNA bearing upstream open reading frames that favor 5' cap-independent translation [ 3 ]. (biomedcentral.com)
The eIF2α kinases phosphorylate Ser51 of eIF2α which leads to suppression of global protein synthesis but selective enhancement of translation of some mRNAs, such as that encoding ATF4. (biomedcentral.com)
The m 7 G-cap of the mRNA is recognized by the 43S translation preinitiation complex comprised of the 40S ribosomal subunit and the eIF2-GTP-Met-tRNAi ternary complex. (biorxiv.org)
Upon stress, phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) decreases the available ternary complex, resulting in reduced translation initiation from the start codons of uORFs (uAUGs) and prolonged scanning of the preinitiation complex to translate the downstream main open reading frames (mORFs) to promote cell survival 12 - 15 . (biorxiv.org)
This raises questions: How is translation of these uORF-containing mRNAs regulated if not by phosphorylation of eIF2α? (biorxiv.org)
PERK, (a component of the integrated stress response) then phosphorylates the eukaryotic translation initiation factor 2 subunit −α (eIF2α), which results in global translational arrest. (encyclopedia.pub)
Of special interest are the translation initiation factors eIF2, a GTPase that binds methionyl-tRNA to the ribosome, and eIF5B, a second GTPase that catalyzes ribosomal subunit joining in the final step of translation initiation. (nih.gov)
The first step of protein synthesis is binding of the initiator Met-tRNA to the small ribosomal subunit by the factor eIF2, which is composed of three subunits. (nih.gov)
The gamma subunit of eIF2 is a GTPase that resembles the bacterial translation elongation factor EF-Tu. (nih.gov)
In genetic and biochemical studies, we found that the mutation disrupts eIF2 complex integrity, impairs general translation, alters translational control of mRNAs encoding key regulatory proteins, and reduces the fidelity of translation start codon selection. (nih.gov)
The findings directly link intellectual disability with impaired translation initiation and provide a mechanistic basis for the human disease resulting from partial loss of eIF2 function (Reference 1). (nih.gov)
Phosphorylation of eIF2alpha converts eIF2 from a substrate to an inhibitor of its guanine-nucleotide exchange factor eIF2B. (nih.gov)
Activated Benefit phosphorylates and inhibits eukaryotic initiation aspect 2 (eIF2) resulting in global translational attenuation. (cgp60474.com)
PERK phosphorylates eIF2, which blocks the binding of the initiator Met-tRNA to the ribosome leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. (russnewton.com)
These viruses stimulate canonical cap-dependent initiation of translation by promoting eukaryotic translation initiation factor 4 subunit F (eIF4F) assembly while simultaneously stimulating the dephosphorylation of eIF2α to avoid suppression Timosaponin b-II of protein translation (7 8 Alternatively two DNA viruses that replicate in the cytosol poxviruses and asfarviruses have been suggested to promote viral translation by recruiting host translational factors to the sites of viral replication (9 -11). (biongenex.com)

Phosphorylation of the eIF2alpha subunit is a common mechanism for down-regulating protein synthesis under stress conditions. (nih.gov)
In keeping with these colocalization research σNS was discovered to associate with both eukaryotic translation initiation aspect 3 subunit A (eIF3A) as well as the ribosomal subunit pS6R. (biongenex.com)
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)
Initiation begins with the assembly of a pre-initiation complex (PIC) in which the small ribosomal subunit is joined by several protein initiation factors (eIFs). (vassar.edu)

The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. (ox.ac.uk)
p97) is an essential regulator of protein degradation in multiple pathways and has emerged as a target for cancer therapy. (ox.ac.uk)
During ER stress-a state of functional imbalance-adaptive and restorative programs such as the unfolded protein response (UPR) and ER-associated protein degradation (ERAD), or autophagy, come into play [ 12 ] [ 13 ] . (encyclopedia.pub)
This apparent increase in p27 protein expression might have been due to either increased synthesis or decreased degradation, or a combination of both [ 1 ]. (biomedcentral.com)
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)
Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication. (virosin.org)
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)
By then targeting host translation initiation factors for degradation these viruses can promote their own translation to the detriment of the host (5 6 In contrast many DNA viruses produce mRNAs that resemble host mRNAs. (biongenex.com)

We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. (nih.gov)
In the brain, mRNA translation is a critical cellular mechanism, providing tailored responses to the different demands of general homeostasis and synaptic plasticity, and is regulated in both its initiation and elongation phases [ 6 ]. (nature.com)
Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). (avivasysbio.com)
impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). (avivasysbio.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)
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)
Summary We conclude that mTOR has a part in maintaining prolonged pain claims via mRNA translation and thus protein synthesis. (researchensemble.com)
More recently, Co-workers and Cost have got implicated particular spine mRNA translation pathways in formalin-induced behavioural hypersensitivity [9]. (researchensemble.com)
EIF2AK2 plays a critical role in mRNA translation, cell proliferation and apoptosis. (signalchem.com)

In the PERK arm, during stress, PERK dissociates from the chaperone protein, binding immunoglobulin protein/glucose-regulated protein 78 (BiP/GRP78), and undergoes dimerization and phosphorylation. (encyclopedia.pub)
Cyclic mechanical load causes global translational arrest in articular chondrocytes: a process which is partially dependent upon PKR phosphorylation. (ox.ac.uk)
Phosphorylation of PKR occurred in explants following cyclic load and inhibition of PKR modestly reversed suppression of newly synthesised proteins suggesting that PKR, at least in part, was responsible for loading induced translational arrest. (ox.ac.uk)
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)
123 , 3893-900 By creating a series of mutations in the protein lamin A, Akt1 phosphorylation sites were determined. (promegaconnections.com)

A key element regulating the elongation phase is the eukaryotic elongation factor (eEF2) pathway [ 8 ]. (nature.com)
studies revealed that active translation occurs within VF and that ribosomal subunits and proteins required for translation initiation elongation termination and recycling localize to the factory. (biongenex.com)

To identify common features shared by transcripts with stress-upregulated translation efficiency (TE-up), we first performed high-resolution ribosome-sequencing in Arabidopsis during pattern-triggered immunity and found that TE-up transcripts are enriched with upstream open reading frames (uORFs). (biorxiv.org)
Upon immune induction, there is an overall downshift in ribosome occupancy at uAUGs, accompanied by enhanced translation of main ORFs (mORFs). (biorxiv.org)
Moreover, recent global ribosome-sequencing (Ribo-seq, sequencing of ribosome-protected RNA fragments) studies have shown that uORFs are a prevalent feature in eukaryotic mRNAs, not limited to these few well-studied examples 19 - 21 . (biorxiv.org)
We are characterizing eIF2gamma mutations that are associated with a novel X-linked intellectual disability syndrome, and we are investigating the function of the translation factor eIF5A with a focus on its ability to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates such as proline. (nih.gov)
Met-tRNAi Functions in Directing the Scanning Ribosome to the Start Site of Translation, and the ribosomes translate RNA into proteins that are then folded.If that folding goes wrong, for example because of a DNA mutation, a translation error, too much or too little of some chemicals or chemicals replacing amino acids, (partly)unfolded proteins remain in the RER. (russnewton.com)
Expression of the Escherichia coli tryptophanase operon depends on ribosome stalling during translation of the upstream TnaC leader peptide, a process for which interactions between the TnaC nascent chain and the ribosomal exit tunnel are critical. (cipsm.de)
We determined subnanometer-resolution cryo-electron microscopy structures of eukaryotic ribosome-Sec61 complexes. (cipsm.de)
The E. coli S30 T7 High-Yield Protein Expression System is designed to express up to 500μg/ml of protein in 1 hour from plasmid vectors containing a T7 promoter and a ribosome binding site. (promegaconnections.com)
online) Examines the effect of upstream codon sequence/length on the correct ribosome binding and translation initiation of the pfrA protein. (promegaconnections.com)
Translation initiation is the process that assembles the ribosome, the molecular apparatus which translates the genetic code and synthesizes the corresponding protein. (vassar.edu)
Assembly of the ribosome on a specific mRNA during initiation is an important step for regulating translation. (vassar.edu)
To investigate the role of eIF3 in translation initiation, we employ ribosome profiling, which enables us to learn the position of each translating ribosome on every mRNA in living cells. (vassar.edu)

Programmed cell death 4 (PDCD4) is an important tumor suppressor in the development of various human cancers [1] and inhibits translation rather than transcription. (plos.org)

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)
The mechanisms involved in the stress-induced translation have been investigated for a small number of key transcription factors (for example, yeast general control nondepressible 4 (GCN4) 12 and mammalian activating transcription factor 4 (ATF4) 13 ), whose translation is normally inhibited by the uORFs in the 5' leader sequences of their mRNAs. (biorxiv.org)
Under these conditions only certain mRNAs such as those encoding activating transcription factor 4 (ATF4) are translated, in order to maintain functions important for cell survival. (encyclopedia.pub)
Finally, (d) global hypomethylation of 5'-m 7 G cap of mRNAs could also up-regulate expression of p27. (biomedcentral.com)
Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. (avivasysbio.com)
Nevertheless, specific mRNAs gain a selective benefit for translation under these circumstances e.g. activating transcription aspect (ATF4). (cgp60474.com)
Launch Translation of mRNAs by eukaryotic cells is Timosaponin b-II certainly a complicated energy-dependent process that may be quickly suppressed in response to mobile stressors such as for example negative energy stability starvation growth aspect withdrawal hypoxia proteins misfolding and viral contamination (reviewed in reference 1). (biongenex.com)
It could concentrate the factors needed for translation of viral mRNAs close to the sites of viral transcription potentially linking the two processes and increasing the efficiency of gene expression as occurs in prokaryotes (12). (biongenex.com)

Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. (nih.gov)
The integrated stress response (ISR) is an adaptive signaling pathway that contributes to the biology of a number of hematologic malignancies since they are inherently prone to numerous cellular stresses [ 2 ]. (biomedcentral.com)
The ISR (Fig. 1 ) is a complex signaling pathway that regulates cellular responses to stress stimuli and enables either adaptation or the instigation of cell death mechanisms [ 2 ]. (biomedcentral.com)
The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. (mdpi.com)
Mutant huntingtin (mHtt) aggregates and affects cellular processes in multiple ways [ 2 ] . (encyclopedia.pub)
The cellular mechanisms by which articular cartilage responds to load are poorly understood, but such responses may involve regulation at the level of protein translation rather than synthesis of mRNA. (ox.ac.uk)
Aggregated misfolded proteins in the ER cause cellular stress, which if unresolved can lead to cell death. (distantreader.org)
The different building blocks can affect the complementarity of the RNA molecules, alter their structure, and enable the binding of specific proteins that mediate various biochemical and cellular outcomes. (pharmaceuticalintelligence.com)
This enabled the diversified complementarity and secondary structures that allow RNA species to specifically interact with other components of the cellular machinery such as DNA and proteins. (pharmaceuticalintelligence.com)
We study the mechanism and regulation of protein synthesis, focusing on GTPases and protein kinases that control this fundamental cellular process. (nih.gov)
We also investigate stress-responsive protein kinases that phosphorylate eIF2alpha, viral regulators of these kinases, and how cellular phosphatases are targeted to dephosphorylate eIF2alpha. (nih.gov)
To this end, we develop a computational method for dissecting the global human interactome into tissue-specific cellular networks. (biomedcentral.com)
This dependence needs viruses to progress systems to coerce the web host translational equipment into synthesizing viral protein when confronted with ongoing cellular tension replies that suppress global proteins synthesis. (biongenex.com)
Whereas regulating gene expression in multicellular organisms allows for cellular differentiation, in single-celled organisms like prokaryotes, it primarily ensures that a cell's resources are not wasted making proteins that the cell does not need at that time. (pressbooks.pub)

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)
We discovered herein that blocking the PI3KÎ´ pathway pharmaceutically to varying degrees can generate T cells with increasingly heightened stemness properties, based on the progressive enrichment of the transcription factors Tcf-1 and Lef-1. (bvsalud.org)
Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
This latter finding is likely to preclude the existence of cryptic transcription factor binding site(s) in the 5'-untranslated region of p27 gene. (biomedcentral.com)
The unprecedently speedy development of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was enabled with previous innovations in nucleoside modifications during in vitro transcription and lipid nanoparticle delivery materials of mRNA. (mdpi.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)
The inhibition of eIF2B impairs general translation, slowing the growth of yeast cells and, paradoxically, enhancing the translation of the GCN4 mRNA (GCN4 is a transcription factor) required for yeast cells to grow under amino-acid starvation conditions. (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)
Activated ATF6 mediates transcription of genes encoding ER chaperone proteins also. (cgp60474.com)
The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. (cipsm.de)
This is attained by spinally administering the overall transcription inhibitor actinomycin D and the overall translation inhibitor anisomycin spinally, to formalin shot in to the hind paw prior. (researchensemble.com)
The protein expression system provides an extract that contains T7 RNA polymerase for transcription and is deficient in OmpT endoproteinase and lon protease activity. (promegaconnections.com)
however, gene expression in eukaryotes is more complicated because of the temporal and spatial separation between the processes of transcription and translation. (pressbooks.pub)

In response to immune induction, uORF-inhibition is alleviated by three Ded1p/DDX3X-homologous RNA helicases which unwind the RNA structures, allowing ribosomes to bypass the inhibitory uORFs and upregulate defence protein production. (biorxiv.org)
Once protein is translated by ERassociated ribosomes, it enters into the ER lumen and is folded in a chaperon-assisted manner. (distantreader.org)

Sensors and effectors are coupled as specific domains of single proteins in PERK, PKR and IRE1. (ucsb.edu)

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)
Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)

In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV). (prolekarniky.cz)
The single genomic RNA codes for two replication proteins, p33 and p92 pol , which are sufficient to support TBSV replicon (rep)RNA replication in yeast ( Saccharomyces cerevisiae ) model host [13] , [14] . (prolekarniky.cz)
We use molecular-genetic and biochemical studies in yeast and human cells to dissect the structure-function properties of translation factors. (nih.gov)

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)
This reaction can temporarily be beneficial, but if the ER stress is prolonged and severe, the UPR can result in cell death through the activation of multiple apoptotic signaling cascades, including CHOP (the CCAAT/enhancer-binding protein homologous protein), also known as GADD153-mediated pathway (growth arrest and DNA damage gene 153), TRAF2 (IRE1/tumor necrosis factor receptor-associated factor 2-mediated pathway), and Ca2+-dependent pathway. (russnewton.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)

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)
Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97. (ox.ac.uk)
Despite the stringent regulation around protein folding and redundancy within the chaperone-assisted folding process, both endogenous and exogenous triggers can disrupt the ER homeostasis and increase protein misfolding. (distantreader.org)
The ER tension response, also called the unfolded proteins response (UPR), is certainly a complicated signaling network initiated to revive regular ER homeostasis by lowering protein fill and increasing proteins folding capability. (cgp60474.com)

The SAR studies described herein support the proposed pharmacology of ISRIB analogues as binding across a symmetrical protein-protein interface formed between protein subunits of the dimeric eIF2B heteropentamer. (ucsf.edu)

They both exert regulatory control by shutting down protein synthesis, turning on genes, and degrading transcripts. (ucsb.edu)
Analyzing the human transcriptome in this way, we identified more than 12,000 methylated sites in mRNA molecules derived from approximately 7,000 protein-coding genes. (pharmaceuticalintelligence.com)
Comparative analysis of these pathways relies on network alignment methods, much the same way as sequence matching and alignments are used for individual genes and proteins. (biomedcentral.com)

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)

However, a block on protein translation that was itself cytotoxic alleviated stress signaling and reduced cell death triggered by VCP inhibition. (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)
Many of the observed effects of VCP inhibition differed from the effects triggered by proteasome inhibition or by protein misfolding. (ox.ac.uk)
Without stress, these structures are responsible for uORF-mediated inhibition of mORF translation by slowing progression of the translation preinitiation complex to initiate translation from uAUGs, instead of mAUGs. (biorxiv.org)

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)
This study provided evidence that the up-regulation of p27 protein expression is at least in part due to increased synthesis and that this increase fairly faithfully recapitulates the cancer preventive activity of nutritional and chemopreventive anti-cancer agents. (biomedcentral.com)
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)
Plastid-specific ribosomal proteins (PSRPs) have been proposed to play roles in the light-dependent regulation of chloroplast translation. (cipsm.de)

This is called the unfolded protein response (UPR). (russnewton.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)

Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. (prolekarniky.cz)
To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p. (prolekarniky.cz)
Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins. (prolekarniky.cz)
All eukaryotic plus-stranded (+)RNA viruses have similar replication cycles in infected cells. (prolekarniky.cz)
After translation of their mRNA-sense genomic RNA(s), the viral RNA and the viral replication proteins are recruited to the site of viral replication in membranous compartments. (prolekarniky.cz)
This is then followed by (+)-strand synthesis in an asymmetric manner, producing excess amounts of (+)-strand progeny, which is released from replication for other viral processes. (prolekarniky.cz)
For efficient replication, (+)RNA viruses recruit numerous host proteins [1] - [5] . (prolekarniky.cz)
The co-opted host proteins likely affect several steps in viral RNA replication, including the assembly of the replicase complex and/or viral RNA synthesis. (prolekarniky.cz)
However, the functions of host factors in (+)RNA virus replication are known only for a small number of host factors [1] - [9] . (prolekarniky.cz)
Jointly virus-induced compartmentalization from the web host translational equipment represents a technique for infections to spatiotemporally few viral proteins synthesis with viral replication and set up. (biongenex.com)
Compartmentalizing translation within replication sites would likely benefit a virus in several ways. (biongenex.com)

The Golgi apparatus not only plays key roles in the transport, processing, and targeting of proteins, but also functions as a sensor of stress, signaling through the Golgi stress response. (encyclopedia.pub)
BiP (Binding immunoglobulin protein) works as a sensor of unfolded proteins in the ER and regulates the activation of these ER stress transducers. (russnewton.com)

This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. (nih.gov)

Among the identified host proteins are RNA-binding proteins, such as translation factors, ribosomal proteins and RNA-modifying enzymes [1] . (prolekarniky.cz)
He was also Manager Tech Services and Training, Product Manager Restriction/Modifying Enzymes, Product Manager Protein Analysis, and is now Sr. Product Manager for Protein Analysis products. (promegaconnections.com)

The largest and most complex of the eIFs is eIF3, which participates in each phase of translation initiation yet remains poorly understood. (vassar.edu)

We find that hypersensitivity to ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility in the Fmr1 KO. (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)

Under stress conditions, such as nutrition depletion 8 , hypoxia 9 , 10 , or pathogen challenge 11 , global translation is reprogrammed, leading to elevated stress-responsive protein production, but repressed growth-related protein synthesis, which is crucial to the survival and adaptation to stress. (biorxiv.org)

We are also examining the role of the hypusine modification on eIF5A and the role of this factor in gene-specific translational control mechanisms. (nih.gov)

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)

S30 High Yield System was used to characterize the inhibitory effect of Txe toxin on protein expression. (promegaconnections.com)

Additionally, the interaction of PCNA with Pol δ is critical for coordinating its transient replacement by other PCNA partner proteins. (nature.com)
Collectively, this study provides the first evidence that transient levels of the evolutionarily conserved factor RACK1 are critical for adult SC activation and proper skeletal muscle regeneration, favoring the efficient progression of SC from a committed to a fully differentiated state. (sdbonline.org)

The MA ratio decreased in chronic liver patients, which is likely explained by impaired albumin synthesis and oxidative stress, caused by hepatic disorder. (frontiersin.org)

It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. (wikipedia.org)

In the UPR, stress sensors recognize unfolded proteins in the ER lumen and relay this information to the nucleus. (ucsb.edu)

Using in planta nucleotide-resolution mRNA structurome probing, we discovered that this stress-induced switch in translation is mediated by highly structured regions detected downstream of uAUGs in TE-up transcripts. (biorxiv.org)
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)
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)

Among the 140 modified RNA nucleotide variants identified, methylation of adenosine at the N6 position (m6A) is the most prevalent epigenetic mark in eukaryotic mRNA. (pharmaceuticalintelligence.com)

Upon aging, persistent NF-κB signaling promotes WMD in these mice as ultrastructural analysis revealed myelination deficits in the corpus callosum accompanied by impaired myelin protein expression. (biomedcentral.com)

Comprehensive gene expression programs are subsequently initiated, allowing the cell to either resolve the protein folding stress or die trying. (ucsb.edu)
Their studies centered on mice missing delicate mental retardation gene (FMR1), which is another proteins that affects translation mRNA. (researchensemble.com)
Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)

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)

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)

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)
Protein conformation is critically linked to function and often controlled by interactions with regulatory factors. (cipsm.de)

Further studies were conducted to gain some insight into the molecular basis of this increase in the synthesis of p27. (biomedcentral.com)
Albumin with a free thiol on Cys34 is the reduced form and designated as mercaptalbumin (MA), while the isoforms with oxidized Cys34, such as a mixed disulfide with low molecular weight thiols and sulfinic/sulfonic acid, are the oxidized forms, which are designated as non-mercaptalbumin (NA)-1 and NA-2, respectively. (frontiersin.org)

Preliminary studies using either N -methyl- N -nitrosourea (MNU)-induced rat breast cancer model or human breast cancer cell lines in vitro had suggested, but not proved, that nutritional and chemopreventive anti-cancer agents increase p27 protein expression. (biomedcentral.com)
The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase. (prolekarniky.cz)

Furthermore we discover the fact that reovirus nonstructural proteins σNS affiliates with Timosaponin b-II 43S preinitiation complexes on the manufacturer margins suggesting a job for σNS in translation. (biongenex.com)

Anatomy23

Organisms15

Diseases1

Chemicals and Drugs127

Analytical, Diagnostic and Therapeutic Techniques and Equipment21

Phenomena and Processes70

Disciplines and Occupations1

Technology, Industry, Agriculture1

Information Science3

Health Care2

Kinase20

EIF224

Subunit4

Degradation8

MRNA translation9

Phosphorylation5

Elongation2

Ribosome12

Inhibits1

MRNAs8

Cellular14

Transcription13

Ribosomes2

PERK1

Apoptosis2

Yeast3

IRE12

Substrate1

Homeostasis4

Subunits1

Genes3

Target of rapamycin1

Inhibition4

Regulation4

Called the unfolded1

Pancreatic1

Replication11

Sensor2

EIF4E1

Enzymes2

EIFs1

Pathway2

Stress-responsive protein1

Translational control1

Biochemical1

Inhibitory1

Transient2

Oxidative1

Membrane protein1

Nucleus1

Downstream3

Prevalent1

Accompanied by impaired1

Gene3

CHOP1

Synaptic1

Regulatory2

Molecular2

Vitro2

Complexes1