• Almost all eukaryotic mRNAs are polyadenylated, with the exception of animal replication-dependent histone mRNAs. (wikipedia.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 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)
  • Through this interaction, mRNAs and their associative proteins form messenger ribonucleoprotein particles (mRNPs) that are actively transported along the cytoskeleton to intracellular destinations. (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)
  • 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)
  • 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)
  • Further mechanistic studies revealed that these functions were controlled by the eukaryotic initiation factor (eIF) 4E and the mitogen-activated protein kinase (MAPK) interacting protein kinase (MNK) signaling pathways, which regulate which mRNAs will be translated. (lu.se)
  • 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)
  • It results from deletion (removal) or insertion (addition) of one or more nucleotides in DNA that generates altered mRNAs with different effects on protein structure . (online-sciences.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)
  • m 6 A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. (molcells.org)
  • Most of these transcriptomic studies monitor the steady state levels of expressed mRNAs in order to derive the "molecular signatures" of tumors [ 2 ]. (biomedcentral.com)
  • Here we demonstrate that RNA-binding proteins can be used to isolate mRNA populations representing total cell mRNA from specific types of cells, as well as discrete mRNA subpopulations that represent post-transcriptionally regulated subsets of mRNAs that encode functionally related proteins. (biomedcentral.com)
  • For example, we identified subpopulations of mRNAs that are associated with ELAV/Hu RNA-binding proteins that are expressed in specific cell types [ 10 ]. (biomedcentral.com)
  • Moreover, because many different mRNA-binding proteins in specific cell types are known to interact with unique subpopulations of mRNAs encoding functionally related proteins [ 9 - 15 ] they can be informative of the dynamic effects of cells on one another. (biomedcentral.com)
  • In this study, we define a model system for using poly (A) binding protein (PABP) to recover mRNAs from specific cell-types in mixed cell cultures. (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)
  • Currently, the 5'UTR remodeling and activation remain structurally and mechanistically uncharacterized for eukaryotic mRNAs. (illinois.edu)
  • Within the scanning model of translation initiation, reinitiation is a non-canonical mechanism that operates on mRNAs harboring upstream open reading frames. (biomedcentral.com)
  • The RPL24B protein of the large ribosomal subunit, which is encoded by SHORT VALVE1 , likewise fosters translation of uORF-containing mRNAs, for example mRNAs for auxin response transcription factors (ARFs). (biomedcentral.com)
  • Aside from eIF3h, another plant-encoded protein that fosters translation of uORF-containing mRNAs is the large ribosomal protein, RPL24B. (biomedcentral.com)
  • 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)
  • Mitogen-activated protein kinase 8-interacting protein 3 gene (MAPK8IP3) encodes the c-Jun-amino-terminal kinase-interacting protein 3 (JIP3) and is involved in retrograde axonal transport. (bvsalud.org)
  • A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. (bvsalud.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)
  • 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)
  • IRE1 (ERN1) is a protein kinase and endoribonuclease that facilitates cytosolic splicing of (XBP1s) mRNA, thereby Benzylpenicillin potassium enhancing expression of the XBP1s isoform, which induces transcription of genes involved in Benzylpenicillin potassium ER-associated protein degradation (ERAD), lipid synthesis, and protein folding (7, 8). (iwap2018.com)
  • The Parkinson's disease genes pink1 and parkin , which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. (sdbonline.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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Here, we show that eIF4A1, but not eIF4A2, enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. (biorxiv.org)
  • 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)
  • Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
  • For instance, it can be activated by oncogenic mutations of PTEN, VHL, the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. (spandidos-publications.com)
  • Messenger RNA (mRNA) is RNA that has a coding region that acts as a template for protein synthesis (translation). (wikipedia.org)
  • The eIF2B protein helps regulate overall protein production (synthesis) in the cell by interacting with another protein, eIF2. (medlineplus.gov)
  • The eIF2 protein is called an initiation factor because it is involved in starting (initiating) protein synthesis. (medlineplus.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)
  • Proper regulation of protein synthesis is vital for ensuring that the correct levels of protein are available for the cell to cope with changing conditions. (medlineplus.gov)
  • Impairment of eIF2B function makes it more difficult for the body's cells to regulate protein synthesis and deal with changing conditions and stress. (medlineplus.gov)
  • The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis. (bvsalud.org)
  • 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)
  • 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)
  • The purpose of the current study was to determine if inhibition of protein synthesis caused by silvestrol triggers autophagy and apoptosis in cultured human cancer cells derived from solid tumors. (biomedcentral.com)
  • Tight control of protein synthesis is essential for normal cellular function and survival, but unrestrained protein synthesis can promote tumorigenesis. (biomedcentral.com)
  • Therefore, silvestrol's ability to block protein synthesis is of significant interest in potentially treating cancers. (biomedcentral.com)
  • These results indicate that in infected cells, gamma(1)34.5 interacts with and redirects phosphatase to dephosphorylate eIF-2alpha to enable continued protein synthesis despite the presence of activated PKR. (scienceopen.com)
  • The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date. (scienceopen.com)
  • 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)
  • 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)
  • 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)
  • In the pancreatic acinar cell CN plays a role in mediating the action of elevated Ca 2+ to stimulate cell division, pancreatic growth and protein synthesis. (pancreapedia.org)
  • Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). (nih.gov)
  • Our data show that the distinct protein interactions of these highly homologous translation factor paralogs shape protein synthesis during mTORC1 inhibition and provide a unique example of the repressive role of a universal translation activator. (biorxiv.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)
  • 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)
  • Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)
  • Activated Benefit phosphorylates and inhibits eukaryotic initiation aspect 2 (eIF2) resulting in global translational attenuation. (cgp60474.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)
  • PERK is one of four protein kinases that phosphorylate eIF2 in mammals in response to different signals. (elifesciences.org)
  • PERK (EIF2AK3) is the third UPR sensor, which phosphorylates the subunit of eukaryotic initiation Benzylpenicillin potassium factor 2 (eIF2) to direct translational and transcriptional modes of gene expression that regulate ER processing of proteins, metabolism, and the oxidation status of cells (6, 10). (iwap2018.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, (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 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • mRNA and protein expression of ABCG2 and phosphorylation of NF-κB was significantly higher in OXA-R than parental cells. (pka-signal.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)
  • 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)
  • In agreement with this, our data show that, as CCT is required for the correct folding of eIF3h and eIF3i subunits, it indirectly influences gene expression with eIF3i overexpression enhancing both cap-and IRES (internal ribosome entry segment)-dependent translation initiation, whereas eIF3h overexpression selectively increases IRES-dependent translation initiation. (manchester.ac.uk)
  • We uncovered the functions of ABCE proteins Rli1/ABCE1 and Arb1 in PIC assembly and ribosome biogenesis, and identified the tRNA methyltransferase Gcd10/Gcd14, which contributed to the discovery of the TRAMP-mediated RNA surveillance pathway. (nih.gov)
  • The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). (nih.gov)
  • Franckenberg, S., Becker, T. & Beckmann, R. Structural view on recycling of archaeal and eukaryotic ribosomes after canonical termination and ribosome rescue. (nature.com)
  • In all organisms, translation is catalyzed in the ribosome, an extraordinary RNA-protein molecular machine in every living cell. (illinois.edu)
  • Professor Jin and her lab propose that structured 5'UTRs can facilitate translation initiation via sequential remodeling: the 5'UTR undergoes sequential conformational changes that are facilitated by RNA binding proteins and translational factors, which ultimately leads to recruitment of the ribosome for translation of the mRNA. (illinois.edu)
  • At present, initial data from Professor Jin's lab suggests that unique interactions between the 5'UTR, associated proteins and the ribosome lead to formation of transcript-specific translation machinery important for cell physiology. (illinois.edu)
  • According to the canonical model of eukaryotic translation, the ribosome dissociates from the mRNA for good as soon as it has terminated translation at a stop codon. (biomedcentral.com)
  • Once a uORF has been recognized and translated, the ribosome must resume scanning and reacquire its initiation factors in order to recognize the start codon of the main ORF, a process known as reinitiation. (biomedcentral.com)
  • In some genes these proteins add a poly(A) tail at one of several possible sites. (wikipedia.org)
  • Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. (nih.gov)
  • Activated ATF6 mediates transcription of genes encoding ER chaperone proteins also. (cgp60474.com)
  • Many proteins are synthesised and folded in the endoplasmic reticulum, and when this organelle is under stress (that is, when it is unable to cope with its workload), three sensors (called PERK, IRE1 and ATF6) send signals to the rest of the cell to perform two tasks: to coordinate various ways of reducing the expression of genes, and to increase the protein folding capacity of the cell to meet demand. (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)
  • In response to ER stress, ATF6 transits from the ER to the Golgi apparatus, where it is cleaved, releasing an N-terminal cytosolic fragment (ATF6-N) that enters the nucleus and activates UPR target genes involved in protein folding and transport (6, 9). (iwap2018.com)
  • Recessive resistance to plant viruses: potential resistance genes beyond translation initiation factors. (ac.ir)
  • The EIF2B1 , EIF2B2 , EIF2B3 , EIF2B4 and EIF2B5 genes provide instructions for making the five parts (subunits) of a protein called eIF2B. (medlineplus.gov)
  • Mutations have been identified in all five of the genes from which the eIF2B protein is produced, although most of these mutations (about 65 percent) occur in the EIF2B5 gene. (medlineplus.gov)
  • 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)
  • Many recent studies have described the use of microarrays to identify genes expressed in different types of cancers (reviewed in [ 1 , 2 ]. (biomedcentral.com)
  • This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
  • 5′-GACGTG-3′) on the promoter region in various target genes ( 1 , 2 ). (spandidos-publications.com)
  • 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)
  • The h subunit of eukaryotic initiation factor 3 (eIF3) boosts translation reinitiation on the uORF-containing mRNA coding for the Arabidopsis bZip transcription factor, AtbZip11, among others. (biomedcentral.com)
  • TDP-43 protein plays an important role in regulating transcriptional repression, RNA metabolism and splicing. (nature.com)
  • In case of partial complementarity, the Ago2 protein fails to cleave, but instead interferes with translation of the target mRNA via its translational repression activity. (thermofisher.com)
  • Dynamic IRE1 splices X-box binding proteins-1 (Xbp)-1 mRNA, translating into a dynamic transcription aspect sXbp-1 that induces ER chaperones and ER-associated proteins degradation. (cgp60474.com)
  • 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)
  • 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)
  • The scanning mechanism of eukaryotic translation initiation. (ac.ir)
  • 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)
  • Translational regulation is arguably least well characterized, and questions concerning the mechanism of translational control abound. (biomedcentral.com)
  • Virions consist, of a central DNA/protein core surrounded in turn by an internal limiting membrane, a viral capsid, and, in the case of those particles that bud from the plasma membrane, an outer viral envelope (Figure 1. (ictv.global)
  • The SNARE complex assembles from vesicular Synaptobrevin-2 as well as Syntaxin-1 and SNAP25 both anchored to the presynaptic membrane. (researchgate.net)
  • New technologies for purifying membrane-bound protein complexes in combination with cryo-electron microscopy (EM) have recently allowed the exploration of such complexes under near-native conditions. (researchgate.net)
  • In particular, polymer-encapsulated nanodiscs enable the study of membrane proteins at high resolution while retaining protein-protein and protein-lip. (researchgate.net)
  • While we and other labs have demonstrated the isolation of mRNA subsets that are potentially co-regulated using RNA binding proteins as reporters of gene expression, methods have not been described that provide information about coordinated posttranscriptional regulation within specific types of cells during tumorigenesis and development. (biomedcentral.com)
  • The average length of 5'UTR sequences has increased over evolution, suggesting that their utilization contributes to the complexity of translational regulation and organism speciation. (illinois.edu)
  • eIF3 (eukaryotic initiation factor 3) is the largest and most complex eukaryotic mRNA translation factor in terms of the number of protein components or subunits. (manchester.ac.uk)
  • For example, they may impair the ability of one of the protein subunits to form a complex with the others, or make it more difficult for the protein to attach to the initiation factor. (medlineplus.gov)
  • The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). (nih.gov)
  • The essential ATP-binding cassette protein ABCE1 splits 80S ribosomes into 60S and 40S subunits after canonical termination or quality-control-based mRNA surveillance processes. (nature.com)
  • 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)
  • The role of translation initiation factors in plants recessive resistance to viruses. (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)
  • Among the eukaryotic translation initiation factors, eIF3 is by far the most complex. (biomedcentral.com)
  • ATF4 activates the transcription of C/EBP homologous proteins (CHOP), considered to mediate palmitate-induced -cell loss of life [10], [11]. (cgp60474.com)
  • As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. (biomedcentral.com)
  • IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. (biomedcentral.com)
  • The carboxyl-terminal 64 aa of gamma(1)34.5 protein are homologous to the corresponding domain of MyD116, the murine growth arrest and DNA damage gene 34 (GADD34) protein and the two domains are functionally interchangeable in infected cells. (scienceopen.com)
  • CnA ( Figure 1 ) contains the catalytic domain, which is homologous to other serine/threonine protein phosphatases (4). (pancreapedia.org)
  • 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)
  • Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways. (medlineplus.gov)
  • Mutations in the eIF (iso) 4G translation initiation factor confer high resistance of rice-to-Rice yellow mottle virus. (ac.ir)
  • 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)
  • Mutations are permanent changes in a DNA sequence, this altered DNA sequence can be reflected by changes in the base sequence of mRNA, and sometimes, by changes in the amino acid sequence of a protein, mutations can cause genetic diseases. (online-sciences.com)
  • and (iii) the alpha subunit in purified eIF-2 phosphorylated in vitro is specifically dephosphorylated by S10 fractions of wild-type infected cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2alpha-P phosphatase activity of gamma(1)34.5- virus infected cells is lower than that of mock-infected cells. (scienceopen.com)
  • 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)
  • 4E-binding proteins (4E-BPs) block the interaction of eIF4E with eIF4G to negatively regulate the formation of the eIF4F complex. (biosyn.com)
  • The Translation Initiating Factor eIF4E and Arginine Methylation Underlie G3BP1 Function in Dendritic Spine Development of Neurons. (antibodiesinc.com)
  • This is also sometimes the case for eukaryotic non-coding RNAs. (wikipedia.org)
  • Many eukaryotic non-coding RNAs are always polyadenylated at the end of transcription. (wikipedia.org)
  • In this study, we investigated the functional role of eukaryotic initiation factor 5B (EIF5B) in hepatocellular carcinoma (HCC) and the underlying mechanisms. (techscience.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)
  • Silvestrol-mediated cell death was attenuated in ATG7-null mouse embryonic fibroblasts (MEFs) lacking a functional autophagy protein. (biomedcentral.com)
  • The codon containing the changed base may become a termination codon, for example, if the serine codon UCA is given a different second base (to become, say, UAA), the new codon causes the termination of translation at that point, this results in protein which is shorter than normal and is usually non-functional. (online-sciences.com)
  • Mass spectrometry combined with X-ray crystallography allows the characterization of cap protein interactions. (biosyn.com)
  • Its major distinguishing features are the ability to bind RNA in a very specific manner through two RNA recognition motifs (RRM) and the C-terminal portion of the protein, which includes a glycine-rich domain that is involved in most of the protein interactions described 3 . (nature.com)
  • This region contains a glutamine/asparagine (Q/N) prion-like domain that participates in protein-protein interactions and in the TDP-43 aggregation process 4 , 5 . (nature.com)
  • Our results elucidate that mitochondria critically require a high level of translational accuracy at Thr codons and highlight the cellular dysfunctions and imbalance in tissue homeostasis caused by mitochondrial mistranslation. (cnrs.fr)
  • 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)
  • In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
  • 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)
  • 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)
  • 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)
  • Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen and vital to many aspects of cancer biology. (spandidos-publications.com)
  • The codon containing the changed base may code for the same amino acid , for example, if the serine codon UCA is given a different third base (to become, say, UCU), it still codes for serine, therefore, this termed a silent mutation without any effect on the protein structure. (online-sciences.com)
  • Calcineurin (CN) is a Ca 2+ /calmodulin dependent serine/threonine protein phosphatase first identified in brain and also known as protein phosphatase 2B (PP2B). (pancreapedia.org)
  • 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)
  • The eIF-2alpha-P phosphatase activities are sensitive to inhibitor 2. (scienceopen.com)
  • 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)
  • Structural complexes between proteins and their substrates can be studied in the gas-phase to determine equilibrium dissociation constants. (biosyn.com)
  • Although some virion-associated proteins such as the major capsid protein, comprise structural elements of the particle, others serve catalytic or regulatory roles, e.g., the virion-associated transactivator of immediate-early transcription. (ictv.global)
  • Structural organization of essential iron-sulfur clusters in the evolutionarily highly conserved ATP-binding cassette protein ABCE1. (nature.com)
  • Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. (expasy.org)
  • ER stress cross-talks to the mitochondrial or intrinsic death pathway via p53-upregulated modulator of apoptosis (Puma) and JNK-dependent upregulation of the Death protein (DP5) [27]. (cgp60474.com)
  • The ER is sensitive to the perturbations in protein homeostasis through a stress-sensing pathway known as the unfolded protein response (UPR). (iwap2018.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)
  • Ago proteins are broadly expressed in somatic cells, associate with miRNAs and are key actors in different RNA silencing pathways. (thermofisher.com)
  • the signal from IRE1 is relayed via a protein called XBP1. (elifesciences.org)
  • C) Lysates were prepared from the cells and IRE1, GFP, or actin protein levels were measured by immunoblot analyses using specific antibodies. (iwap2018.com)
  • We further identify a novel role for the host ER stress sensor protein IRE1 in pathogenesis. (iwap2018.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)
  • Hopfner, K.P. Invited review: architectures and mechanisms of ATP binding cassette proteins. (nature.com)
  • In the present study, we show that the eukaryotic cytosolic chaperonin CCT [chaperonin containing TCP-1 (tailless complex polypeptide 1)] binds to newly synthesized eIF3b and promotes the correct folding of eIF3h and eIF3i. (manchester.ac.uk)
  • Importantly, pro-tumoral perivascular TAMs in breast cancer (BC) are associated with poor prognosis and increased risk of distant metastasis ( Figure 2 ). (lu.se)
  • Metastasis marker proteins also downregulated in OXA-R cells. (pka-signal.com)
  • Proofreading (editing) of mischarged tRNAs by cytoplasmic aminoacyl-tRNA synthetases (aaRSs), whose impairment causes neurodegeneration and cardiac diseases, is of high significance for protein homeostasis. (cnrs.fr)