• 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)
  • Activated Benefit phosphorylates and inhibits eukaryotic initiation aspect 2 (eIF2) resulting in global translational attenuation. (cgp60474.com)
  • 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)
  • 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)
  • 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)
  • 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 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • The RNA helicase eIF4A and the scaffold protein eukaryotic translation initiation factor 4G (eIF4G) and the capping protein eIF4E are part of the complex that loads the mRNAs onto the 40 S ribosomal subunit, together with eIF3. (biosyn.com)
  • The 'closed-loop' model explains that the induction of 5'- to 3'-proximity of mRNAs requires the initiation factors eIF4E, eIF4G, and PABP. (biosyn.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Melanoma also frequently exhibits enhanced activation of receptor tyrosine kinases like epidermal growth factor receptor (EGFR) and MET, as well as BRAF and small G proteins such as Ras [ 2 ]. (biomedcentral.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)
  • 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)
  • The role of translation initiation factors in plants recessive resistance to viruses. (ac.ir)
  • Mutations in the eIF (iso) 4G translation initiation factor confer high resistance of rice-to-Rice yellow mottle virus. (ac.ir)
  • Resistance to Plum pox virus strain C in Arabidopsis thaliana and Chenopodium foetidum involves genome-linked viral protein and other viral determinants and might depend on compatibility with host translation initiation factors. (ac.ir)
  • Recessive resistance to plant viruses: potential resistance genes beyond translation initiation factors. (ac.ir)
  • The scanning mechanism of eukaryotic translation initiation. (ac.ir)
  • 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)
  • The Translation Initiating Factor eIF4E and Arginine Methylation Underlie G3BP1 Function in Dendritic Spine Development of Neurons. (antibodiesinc.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)
  • Franckenberg, S., Becker, T. & Beckmann, R. Structural view on recycling of archaeal and eukaryotic ribosomes after canonical termination and ribosome rescue. (nature.com)
  • 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)
  • Notably, the movement implies a collision with A-site factors, thus explaining the splitting mechanism. (nature.com)
  • In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. (mdpi.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)
  • In this study, we investigated the functional role of eukaryotic initiation factor 5B (EIF5B) in hepatocellular carcinoma (HCC) and the underlying mechanisms. (techscience.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)
  • Sustained expression of Hnf6 also results in downregulation of the β-cell-specific transcription factor MafA and a decrease in total pancreatic insulin. (diabetesjournals.org)
  • Mutant huntingtin (mHtt) aggregates and affects cellular processes in multiple ways [ 2 ] . (encyclopedia.pub)
  • 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)
  • 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 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)
  • These RNAi analyses were quantified by Western blots (using anti-p68 RNA helicase and anti-EIF 2 α ) and Fluc/Rluc 3'UTRs/CDS assays. (lidsen.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)
  • The major risk factors associated with HCC development and progression include chronic hepatitis B or C virus infections, high alcohol consumption, and activation of oncogenes [ 2 ]. (techscience.com)
  • In addition, silvestrol blocked progression through the cell cycle at the G 2 -phase. (biomedcentral.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)
  • Biosynthesis of spermidine (Spd) is critical for cell growth as it is required for hypusination-mediated activation of eukaryotic initiation (translational) factor 5A (eIF5A). (usda.gov)
  • Translational control by the Epstein-Barr virus small RNA EBER-1. (wikidata.org)
  • Translational control in positive strand RNA plant viruses. (ac.ir)
  • Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (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 Onecut homeodomain transcription factor hepatic nuclear factor 6 (Hnf6) is necessary for proper development of islet β-cells. (diabetesjournals.org)
  • In addition to the cis -elements in its 3′UTR and trans -acting factor Staufen, posterior localization of oskar mRNA requires deposition of exon junction complex (EJC) in its first exon through splicing ( Hachet and Ephrussi, 2004 ). (frontiersin.org)
  • Figure 2: Conformational transition of NBSs of ABCE1 from pre-splitting to post-splitting state. (nature.com)
  • manuscripts are undertaken in 15.0 days from acceptance to publication (median values for papers published in this journal in the second half of 2021, 1-2 days of FREE language polishing time is also included in this period). (lidsen.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)
  • Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. (biomedcentral.com)
  • To further evaluate the effects of the overexpression of the Bcl-2 homologue Buffy , this study analysed lifespan and climbing ability in both parkin -RNAi- and Pink1 -RNAi-expressing flies. (sdbonline.org)
  • Distinct and overlapping factors are involved in lifespan extension by bacterial DR (bDR) and liquid DR (lDR) - two protocols of bacterial dilution in liquid cultures. (biomedcentral.com)
  • Synaptobrevin-2 is one of the key players of neuronal exocytosis. (researchgate.net)
  • 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)
  • To achieve this, cells of in vitro produced bovine embryos were traced from the 2-cell stage to the blastocyst stage. (bioone.org)
  • ii) identifying a higher-order assembly of initiation factors 1, 2, 3, and 5-the multifactor complex (MFC)-and elucidating its roles in PIC assembly and accurate start codon selection. (nih.gov)
  • The SNARE complex assembles from vesicular Synaptobrevin-2 as well as Syntaxin-1 and SNAP25 both anchored to the presynaptic membrane. (researchgate.net)
  • Additionally, the structure of a native post-splitting complex reveals ABCE1 to be part of the 43S initiation complex, suggesting a coordination of termination, recycling, and initiation. (nature.com)
  • Figure 2: Brown et al. (biosyn.com)
  • A dinuclear metal center composed of one iron and one zinc molecule each lies next to a β sandwich on the active site ( Figure 2 ). (pancreapedia.org)