• We observed that H 2 S can improve left ventricular function and the deposition of myocardial collagen fibers, inhibit pyroptosis, down-regulate the expression of P-eif2α in myocardial tissue, and inhibit cell autophagy by activating the phosphatidylinositol 3-kinase (PI3K)/AKT1 signaling pathway (p (kjpp.net)
  • In addition, angiotensin II (1 μM) H9c2 cardiomyocytes were injured in vitro experiments, and it was also observed that pyroptosis was inhibited after H 2 S (400 μmol/kg) intervention, the expression of P-eif2α in cardiomyocytes was significantly down-regulated, and the PI3K/AKT1 signaling pathway was activated at the same time. (kjpp.net)
  • Therefore, increasing the expression of P-eif2α reverses the activation of the PI3K/AKT1 signaling pathway by H 2 S. In conclusion, these findings suggest that exogenous H 2 S can ameliorate MF in rats with AAC by inhibiting pyroptosis, and the mechanism may be associated with inhibiting the phosphorylation of eif2α and activating the PI3K/AKT1 signaling pathway to inhibit excessive cell autophagy. (kjpp.net)
  • In the HCC cells, activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing. (techscience.com)
  • 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)
  • GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that senses amino acid deficiency through binding to uncharged transfer RNA (tRNA). (wikipedia.org)
  • GCN2 is the only known eukaryotic initiation factor 2α kinase (eIF2α) in Saccharomyces cerevisiae. (wikipedia.org)
  • 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)
  • Early accomplishments of the SNCGE in this area include discovering the novel regulatory mechanism that induces translation of GCN4 mRNA via small upstream ORFs (uORFs) in the mRNA leader by phosphorylation and inhibition of eIF2 by the kinase Gcn2, now understood to regulate expression of key transcription factors (Atf4 and Atf5) in mammals and implicated in learning and memory. (nih.gov)
  • We also made key contributions to identifying the eIF2α kinase Gcn2 and elucidating its regulation by amino acids, via allosteric control of kinase activity by uncharged tRNAs and Gcn2 regulatory domains, and by the TOR pathway through Gcn2-Ser577 phosphorylation. (nih.gov)
  • Since ER stress can cause differential modulation of the unfolded protein response (UPR), which includes the inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) pathways, these were individually tested in 3a-expressing cells. (nih.gov)
  • Equally importantly, ISRIB also prevented the reduction in overall protein synthesis that is normally observed within cells when eIF2 phosphorylation is high following integrated stress response kinase activation. (elifesciences.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)
  • Hepatocyte growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced proliferation, but tumor necrosis factor alpha (TNF-alpha) receptor has not been affected. (biomedcentral.com)
  • 2004) S6K1(−/−)/S6K2(−/−) mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. (concordia.ca)
  • 1998) Regulation of the p70 S6 kinase by phosphorylation in vivo. (concordia.ca)
  • Stress-activated protein kinase pathway functions to support protein synthesis and translational adaptation in response to environmental stress in fission yeast. (ox.ac.uk)
  • Protein synthesis was further reduced in mutants disrupting the SAPK pathway, including the mitogen-activated protein kinase Wis1 or the mitogen-activated protein kinase Spc1/Sty1, suggesting a role for these stress response factors in this translational control. (ox.ac.uk)
  • Disruption of Wis1 or Spc1 kinase or the downstream bZip transcription factors Atf1 and Pap1 resulted in a marked increase in eIF2alpha phosphorylation which was dependent on the eIF2alpha kinases Hri2 and Gcn2. (ox.ac.uk)
  • Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m 6 A processing. (molcells.org)
  • Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the PI3 kinase pathway. (assaygenie.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)
  • 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)
  • Enhancers are Cis DNA elements that facilitate or enhance initiation of transcription at the promoter, they interact with gene regulatory proteins or trans-factors (so termed because they are produced by other genes ) and increase the rate of expression. (online-sciences.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)
  • PERK works by phosphorylating a protein called eIF2 that is needed to start the translation of messenger RNA into strings of amino acids, which fold to form proteins. (elifesciences.org)
  • Paradoxically, these stress-induced signalling events also enhance the translation of the messenger RNAs for some proteins, including a transcription factor called ATF4 that modulates the expression of various genes, to ameliorate the perceived stress. (elifesciences.org)
  • m 6 A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. (molcells.org)
  • The m 6 A-modified RNAs then recruit m 6 A-binding proteins (readers) that guide these RNAs for RNA biogenesis processes such as pre-mRNA splicing, nuclear export, stabilization, degradation, and translation. (molcells.org)
  • In the glioma cells, EIF5B promotes cell survival by enhancing the translation of several IRES-containing mRNAs including those encoding anti-apoptotic proteins such as XIAP and Bcl-xL [ 4 ]. (techscience.com)
  • Heterogeneous population of RNA granules serve as motile units to translocate, store, translate, and degrade mRNAs in the dendrites contain cis -elements and trans -acting factors such as RNA-binding proteins and microRNAs to convey stimulus-, transcript-specific local translation. (frontiersin.org)
  • This gene encodes one member of a family of translation repressor proteins. (assaygenie.com)
  • 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)
  • Thus, GCGs contain proteins involved in translation initiation, translation control, and mRNA decay, which is consistent with their proposed role in the regulation ofs maternal mRNA expression. (rupress.org)
  • ADP-ribosylation is a post-translational modification of proteins that occurs mostly in response to cellular stress and is catalysed by members of the diverse poly-ADP-ribose (PAR) polymerase (PARP/ARTD) family. (cipsm.de)
  • Like transcription, translation is controlled by proteins that bind and initiate the process. (openstax.org)
  • 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)
  • Levels of proteins, including Cyt C, Bcl-2/BAX, and Nrf2 /HO-1-associated proteins, were determined by western blotting and immunofluorescence. (sdbonline.org)
  • 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)
  • The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase), belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. (biomedcentral.com)
  • 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)
  • 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)
  • This raises questions: How is translation of these uORF-containing mRNAs regulated if not by phosphorylation of eIF2α? (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)
  • EIF5B (Eukaryotic Translation Initiation Factor 5B) is a conserved eukaryotic translation factor that mediates association of the 40S and 60S ribosomal subunits during eukaryotic translation initiation, and modulates the cell cycle progression by regulating the translation of upstream open reading frames (uORF)-containing mRNAs such as p27 and p21 [ 3 ]. (techscience.com)
  • The existence of mRNAs retaining both nuclear cap binding protein and EJC in the distal sites of neuronal processes suggests that some localized mRNAs have not yet undergone the "very first translation," which contribute to the spatio-temporal regulation of gene expression. (frontiersin.org)
  • The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. (assaygenie.com)
  • Some mRNAs are programmed for immediate translation, a process that remodels the protein coat and assembles a polysome. (rupress.org)
  • After productive translation, mRNAs are deadenylated, polysomes are disassembled, and the mRNA is either degraded or stored. (rupress.org)
  • Other mRNAs are programmed for delayed translation, allowing transcripts to be transported or stored until developmental or environmental cues call for their translation. (rupress.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • In starvation conditions, the reinitiating ribosomes bypass uORFs 2-4 and reinitiate at GCN4 instead, owing to lowered availability of the ternary complex (TC)-comprised of initiation factor 2 (eIF2), GTP, and initiator Met-tRNAi-which binds to the small (40S) ribosomal subunit to assemble a 43S preinitiation complex (PIC). (nih.gov)
  • We have also investigated the roles of various eIFs, tRNAi and the 40S subunit in scanning the mRNA 5′ untranslated region and in accurately identifying the AUG initiation codon. (nih.gov)
  • The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and to increase IFNAR1 ubiquitination. (nih.gov)
  • 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)
  • Reduced translation initiation correlated with phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) in wild-type cells. (ox.ac.uk)
  • Co-transcriptional pre-mRNA processing relies on reversible phosphorylation of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II (RNAP II). (cipsm.de)
  • The phosphate and the eIF-2 protein are released from the complex and the large 60S ribosomal subunit binds to translate the RNA. (openstax.org)
  • 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)
  • Phosphorylation of the eIF2alpha subunit is a common mechanism for down-regulating protein synthesis under stress conditions. (nih.gov)
  • Cyclic mechanical load causes global translational arrest in articular chondrocytes: a process which is partially dependent upon PKR phosphorylation. (ox.ac.uk)
  • Cyclic loading caused complete global translational arrest as evidenced by a total suppression of new protein synthesis whilst maintaining mRNA levels. (ox.ac.uk)
  • This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. (assaygenie.com)
  • 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)
  • Different classes of RNA granules share some protein components and may use similar mechanisms to regulate mRNA translation/decay. (rupress.org)
  • GCGs direct the timing of maternal mRNA translation to promote germ cell development in the early embryo and establish the germ line for the next generation. (rupress.org)
  • 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)
  • 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)
  • Conservation of the RNA helicases suggests that mRNA structurome remodelling is a general mechanism for stress-induced translation across kingdoms. (biorxiv.org)
  • We identified the eIF2α phosphatases in yeast and made key contributions to elucidating the mechanism whereby phosphorylated eIF2 inhibits its GDP-GTP exchange factor, eIF2B, defining the catalytic and regulatory subcomplexes of eIF2B and their distinct roles in binding phosphorylated or nonphosphorylated eIF2. (nih.gov)
  • As noted above, a key accomplishment of the SNCGE was elucidating the unique mechanism of translational control of GCN4 mRNA. (nih.gov)
  • These findings have helped to illuminate the molecular mechanism of TC recruitment and assembly of 43S PICS at an early stage of the initiation pathway. (nih.gov)
  • These results show that translational control provides a rapid and potentially important mechanism for controlling the synthetic responses of articular chondrocytes in response to different types of mechanical load. (ox.ac.uk)
  • We review the relationship between different classes of these granules and discuss how spatial organization regulates messenger RNA translation/decay. (rupress.org)
  • Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). (omicsdi.org)
  • 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)
  • 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)
  • According to the current model, scanning ribosomes translate the 5′-most uORF (uORF1) and, under non-starvation conditions, reinitiate translation at downstream uORFs 2, 3, or 4 and subsequently dissociate from the mRNA, keeping GCN4 translation repressed. (nih.gov)
  • ISRIB acts downstream of the phosphorylation of eIF2 (eIF2(αP)) and upstream of the activation of ATF4 (green arrow) and the repression of bulk protein synthesis (red down arrow). (elifesciences.org)
  • Collectively the data suggest that EBNA3C interacts with Gadd34, activating the upstream component of the UPR (eIF2α phosphorylation) while preventing downstream UPR events (XBP1 activation and ATF6 cleavage). (scienceopen.com)
  • It has been hypothesized, that UV induces nitric oxide synthase activation and NO. production, which leads to the activation of GCN2 and that the cell cycle regulation by GCN2 is independent of eIF2α phosphorylation. (wikipedia.org)
  • We previously exploited this fact to isolate mutations in subunits of eIF2B that constitutively derepress GCN4 (Gcd− phenotype) by lowering TC assembly in the absence of eIF2 phosphorylation. (nih.gov)
  • 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)
  • 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)
  • 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)
  • Current concepts suggest that a limited number of molecular alterations involving oncogene activation and tumor suppressor inhibition are responsible for initiation of cancer. (biomedcentral.com)
  • Only the PERK pathway was found to be activated in 3a-expressing cells based on (1) increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) and inhibitory effects of a dominant-negative form of eIF2alpha on GRP78 promoter activity, (2) increased translation of activating transcription factor 4 (ATF4) mRNA, and (3) ATF4-dependent activation of the C/EBP homologous protein (CHOP) gene promoter. (nih.gov)
  • These findings suggest a role for the SAPK pathway in supporting translation initiation and facilitating adaptation to environmental stress in part through reducing eIF2alpha phosphorylation in fission yeast. (ox.ac.uk)
  • Phosphorylation of eIF2alpha converts eIF2 from a substrate to an inhibitor of its guanine-nucleotide exchange factor eIF2B. (nih.gov)
  • 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)
  • Subsequent tests convincingly showed that this molecule does not prevent the activation of PERK or the phosphorylation of eIF2α. (elifesciences.org)
  • Distinct cellular stresses cause the phosphorylation and activation the eIF2α kinases PERK, PKR, GCN2 and HRI. (biomedcentral.com)
  • Methylases are present at the level of DNA metabolism, RNA metabolism and protein post-translational modifications [ 2 - 4 ]. (biomedcentral.com)
  • It inactivates eIF2α by phosphorylation at Serine 51 under conditions of amino acid deprivation, resulting in repression of general protein synthesis whilst allowing selected mRNA such as GCN4 to be translated due to regions upstream of the coding sequence. (wikipedia.org)
  • 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)
  • The actions of these four kinases in response to stress-phosphorylation of eIF2 and increased translation of ATF4-is termed the integrated stress response (ISR). (elifesciences.org)
  • Translation is again initiated, uORF2,3 or 4 translated and the 40S Subunits subsequently dissociate from GCN4 mRNA. (wikipedia.org)
  • Hence, GCN4 translation is an in vivo indicator of impaired TC loading on 40S subunits. (nih.gov)
  • GCN2 inhibits general translation by phosphorylation of eIF-2α at serine 51 within 15 min of amino acid deprivation, which then subsequently increases the affinity for the guanine exchange factor eIF2B to sequester eIF-2α leading to reduced formation of the ternary complex (TC) consisting of eIF2, GTP and the initiator Met-tRNA required for translation initiation. (wikipedia.org)
  • 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)
  • Interaction of this protein with eIF4E inhibits complex assembly and represses translation. (assaygenie.com)
  • The molecular mechanisms governing this function are not yet known, but a basic zipper transcription factor called ATF4 is a possible candidate. (wikipedia.org)
  • eIF2B, a mediator of general and gene-specific translational control. (medlineplus.gov)
  • 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)
  • In response to environmental changes, signaling pathways rewire gene expression programs through transcription factors. (molcells.org)
  • RNA transport and regulated local translation play critically important roles in spatially restricting gene expression in neurons. (frontiersin.org)
  • Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)
  • Figure 16.13 Gene expression can be controlled by factors that bind the translation initiation complex. (openstax.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)
  • Under some conditions, eIF2B increases protein synthesis by helping to recycle molecules called GTP, which carry energy to the initiation factor. (medlineplus.gov)
  • Under other conditions, it slows protein synthesis by binding tightly to the initiation factor, which converts the eIF2B protein into an inactive form and prevents recycling of GTP. (medlineplus.gov)
  • TC abundance is reduced in starved cells by phosphorylation of eIF2α by Gcn2, converting eIF2 from substrate to inhibitor of its guanine nucleotide exchange factor (GEF) eIF2B. (nih.gov)
  • This two-pronged response involves changes at both the transcriptional level (in the cell nucleus) and the translational level (in the cytoplasm). (elifesciences.org)
  • Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.com)
  • Therefore, the reduction in TC formation resulting from GCN2 activation by amino acid starvation leads to the induction of GCN4 translation. (wikipedia.org)
  • Recently GCN2 has also been implicated in directing eating behavior in mammals by phosphorylating eIF-2α in the anterior Piriform cortex (APC) of the brain. (wikipedia.org)
  • Forty-four Sprague-Dawley rats were randomly divided into control group, AAC group, AAC + H 2 S group, and H 2 S control group. (kjpp.net)
  • We investigated the role of translational control in cyclically (0.5 Hz, 0.1 Hz and 0.05 Hz) and statically loaded porcine articular cartilage explants. (ox.ac.uk)
  • Translational control by the Epstein-Barr virus small RNA EBER-1. (wikidata.org)
  • Mutant huntingtin (mHtt) aggregates and affects cellular processes in multiple ways [ 2 ] . (encyclopedia.pub)
  • In conclusion, the enrichment of AU residues in EBOV 3' UTRs makes them possible targets for cellular ARE-BPs, leading to modulation of RNA stability and translational activity. (bvsalud.org)
  • Low power laser irradiation (LPLI) promotes proliferation of multiple cells, which (especially red and near infrared light) is mainly through the activation of mitochondrial respiratory chain and the initiation of cellular signaling. (biomedcentral.com)
  • 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)
  • These studies exploit a genetic selection for mutations that elevate initiation at near-cognate UUG start codons (Sui− phenotype) or suppress this aberrant initiation event (Ssu− phenotype) (Figure 1B). (nih.gov)
  • We observed that overexpression of the hairpin loop does not activate the phosphorylation of EIF 2 α and, therefore, does not activate PKR interferon-induced apoptosis. (lidsen.com)
  • Characterization of sites of phosphorylation in the interferon-induced phosphoprotein P1 from mouse fibroblasts: evidence for two forms of P1. (wikidata.org)
  • The phosphorylation state of eEF2 is directly linked to synaptic plasticity regulation [ 23 ] and learning, and in the context of cue-induced drug seeking, dephosphorylation of both eEF2 and eIF2α occurs. (nature.com)
  • It acts as a transcription factor and activates several genes required for amino acid synthesis. (wikipedia.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)
  • The eIF2 protein is called an initiation factor because it is involved in starting (initiating) protein synthesis. (medlineplus.gov)
  • Furthermore, LPLI induces the synthesis or release of many molecules, like growth factors, interleukins, inflammatory cytokines and others, which are related to promotive effects of LPLI. (biomedcentral.com)
  • 11. Antion MD, Hou L, Wong H, Hoeffer CA, Klann E (2008) mGluR-dependent long-term depression is associated with increased phosphorylation of S6 and synthesis of elongation factor 1A but remains expressed in S6K-deficient mice. (concordia.ca)
  • In this study, we investigated the functional role of eukaryotic initiation factor 5B (EIF5B) in hepatocellular carcinoma (HCC) and the underlying mechanisms. (techscience.com)
  • 9. Banko JL, Hou L, Poulin F, Sonenberg N, Klann E (2006) Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression. (concordia.ca)
  • Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya), with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and RuBisCO, as an enolase, in some Firmicutes). (biomedcentral.com)
  • Using reporter assays designed to study the function of 3' UTRs in mammalian cells and zebrafish embryos, we show that the tested EBOV 3' UTRs increase reporter activity, either through enhancing the stability or promoting the translation of reporter mRNA, and that this stabilizing effect is conserved across species. (bvsalud.org)
  • Evidence accumulated over the last 2 decades indicates that, during fatal EVD, the infection of antigen-presenting cells (APC) and the dysregulation of T cell immunity preclude a successful transition between innate and adaptive immunity, which constitutes a key disease checkpoint. (bvsalud.org)
  • mRNA and protein expression of ABCG2 and phosphorylation of NF-κB was significantly higher in OXA-R than parental cells. (pka-signal.com)
  • 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)
  • The GADD34 protein may have a similar function in eukaryotic cells. (scienceopen.com)
  • CN has a number of targets but its most prominent are the NFAT (nuclear factor of activated T cells) transcription factors. (pancreapedia.org)
  • Exposure to oxidative stress (H2O2) resulted in a striking reduction in translation initiation in wild-type cells, which was further reduced in spc1- cells. (ox.ac.uk)
  • To achieve this, cells of in vitro produced bovine embryos were traced from the 2-cell stage to the blastocyst stage. (bioone.org)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • Low PDCD4 level was associated with reduced proliferation but not apoptosis or phosphorylation of endothelial nitric oxide synthase caused by pulsatile shear stress to help maintain the homeostasis of endothelial cells. (plos.org)
  • The 4E-BP1 (Phospho-Thr36) Colorimetric Cell-Based ELISA Kit is a convenient, lysate-free, high throughput and sensitive assay kit that can detect 4E-BP1 protein phosphorylation and expression profile in cells. (assaygenie.com)
  • We use molecular-genetic and biochemical studies in yeast and human cells to dissect the structure-function properties of translation factors. (nih.gov)
  • 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)
  • In collaboration with Jon Lorsch's group, we demonstrated that segments/residues in eIF1, eIF1A, tRNAi and 18S rRNA, which are implicated genetically in TC recruitment, also stimulate the rate of this reaction in a fully reconstituted yeast in vitro translation system. (nih.gov)
  • Identification of in vitro 40 S ribosomal S6 phosphorylation sites. (concordia.ca)
  • The preinitiation complex then scans along the 5' leader sequence of the mRNA to initiate translation at a start codon 1 - 3 . (biorxiv.org)
  • Further polysome analyses revealed a role for Spc1 in supporting translation initiation during osmotic stress, and additionally in facilitating translational adaptation. (ox.ac.uk)
  • Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways. (medlineplus.gov)
  • Appropriate protein folding and post-translational modification are crucial for protein function. (distantreader.org)
  • EF-P is present in all bacteria and orthologous to archaeal and eukaryotic initiation factor 5A, yet the biological function has so far remained enigmatic. (cipsm.de)
  • 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)
  • 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)
  • Effects of the presence and absence of amino acids on translation, signaling, and long-term depression in hippocampal slices from Fmr1 knockout mice. (avivasysbio.com)
  • The molecular link between splicing and mRNA localization/local translation has also been demonstrated in mammalian neurons. (frontiersin.org)
  • If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. (openstax.org)
  • An opposing effect of the reduced availability of TC is the induction of GCN4 expression by translational regulation. (wikipedia.org)
  • Phosphorylation of 4E-BP1 disrupts this binding, activating cap-dependent translation. (assaygenie.com)
  • Translational arrest did not occur following static loading and was partly dependent upon the load frequency. (ox.ac.uk)
  • 4E-BP1: binds to eIF4E, preventing its assembly into the EIF4F complex and inhibiting cap-dependent translation. (assaygenie.com)
  • and (5) orthologues of the translation initiation factors eIF4E and eIF5A. (rupress.org)