• In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. (northwestern.edu)
  • We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively. (northwestern.edu)
  • ATF3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation, and loss of ATF3 function significantly lowers stress-induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit implicated in feedback control of the eIF2 kinase stress response. (northwestern.edu)
  • Structure of the delta dII IRES eIF2-containing 48S initiation complex, closed conformation. (expasy.org)
  • 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 addition, activated eIF2α can trigger production of certain proteins called transcription factors, which control gene activity. (medlineplus.gov)
  • The transcription factors regulated by eIF2α control the activity of genes involved in processes that help reduce the stress on the cell. (medlineplus.gov)
  • This event is triggered by eIF2α (eukaryotic translation initiation factor 2α). (chemistryviews.org)
  • Together with eIF2 and GTP, the initiator tRNA binds the P site of the small ribosomal subunit forming the eukaryotic pre-initiation complex. (jove.com)
  • First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). (jove.com)
  • GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. (hindawi.com)
  • 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)
  • The preferential replication of reovirus in cells with activated RAS is due to RAS's ability to inhibit double-stranded RNA-activated protein kinase (PKR), a key sensor that recognizes viral particles and results in abrogation of protein synthesis by phosphorylation of eukaryotic initiation factor 2 alpha (eif2α) [ 7 ]. (biomedcentral.com)
  • eIF3 binds the small ribosomal subunit (40S) at and near its solvent side and serves as a scaffold for several other initiation factors, the auxiliary factor DHX29, and mRNA. (wikipedia.org)
  • In response to amino acid deprivation or UV irradiation, GCN2 phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2a) at Ser51 and induces a delay in entry to S phase of the cell cycle. (rndsystems.com)
  • Upon codon-anticodon recognition, GTP is hydrolyzed and the initiation factors dissociate, allowing the large ribosomal subunit to join the complex and form an intact ribosome. (jove.com)
  • Now, the 50S ribosomal subunit can bind to the initiation complex, with the complete ribosome ready to begin translation. (jove.com)
  • Eukaryotic translation initiation factor 2 (EIF-2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. (thermofisher.com)
  • EIF-2 is composed of three subunits, alpha, beta, and gamma, with the protein encoded by this gene representing the beta subunit. (thermofisher.com)
  • The beta subunit catalyzes the exchange of GDP for GTP, which recycles the EIF-2 complex for another round of initiation. (thermofisher.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)
  • Eukaryotic translation initiation factor 4E (eIF4E) is a cellular target for cadmium toxicity. (cdc.gov)
  • Presently, we have investigated whether the translational proto-oncogene, eukaryotic initiation factor 4E (eIF4E) is a cellular target for cadmium toxicity and carcinogenesis. (cdc.gov)
  • Even though EIF4EBP2 protein binds eIF4E and inhibits translation initiation, growth factors can release this inhibition by a phosphorylation-dependent disruption. (prospecbio.com)
  • This complex recognizes the mRNA by interacting with initiation factors eIF4E bound to the 5' cap, and eIF4G bound to the poly(A) tail-binding proteins. (jove.com)
  • 3 In that clinical trial, some clinical responses associated with the reduction of eukaryotic translation initiation factor 4E (eIF4E) levels were seen. (haematologica.org)
  • Orthologous to human EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3). (zfin.org)
  • Lenvatinib is an oral multi-kinase inhibitor that inhibits mainly vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptor (PDGFR) α, c-KIT, and RET ( 11 ). (spandidos-publications.com)
  • EIF4EBP2 mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase pathway. (prospecbio.com)
  • Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)
  • L'analyse d'image des cartes appariées a permis d'identifier sept protéines qui étaient soit surexprimées, soit sous-exprimées : le récepteur de la protéine kinase C activée, la tubuline alpha (×2), la prostaglandine F2-alpha synthase, la protéine disulfide isomérase, une protéine du transport vésiculaire et une protéine hypothétique. (who.int)
  • Predicted to enable eukaryotic translation initiation factor 2alpha kinase activity. (zfin.org)
  • 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)
  • 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)
  • In humans, eIF3 consists of 13 nonidentical subunits (eIF3a-m) with a combined molecular weight of ~800 kDa, making it the largest translation initiation factor. (wikipedia.org)
  • For instance, while most mammalian eIF3 complexes are composed of 13 subunits, budding yeast's eIF3 has only six subunits (eIF3a, b, c, g, i, j). eIF3 stimulates nearly all steps of translation initiation. (wikipedia.org)
  • All five core subunits of budding yeast's eIF3 are present in heat-induced stress granules, along with several other translation factors. (wikipedia.org)
  • In higher eukaryotes the factor consists of three subunits: alpha, beta, and gamma. (uams.edu)
  • Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. (jove.com)
  • The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and prevent the association of the 40S and 60S ribosomal subunits. (absave.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)
  • We hypothesized that after the rat's plantar incision, the synaptic incorporation of AMPA receptor GluR1 subunits in the DH ipsilateral to the incision would increase due to the interaction between GluK2 and neuropilin tolloid-like 2 (NETO2). (bvsalud.org)
  • In specialized cases of reinitiation following uORFs, eIF3 may remain bound to the ribosome through elongation and termination to promote subsequent initiation events. (wikipedia.org)
  • Recently, our laboratory has demonstrated a novel mechanism for cadmium carcinogenesis that involves the upregulation of translation initiation factor 3 and translation elongation factor-1 delta. (cdc.gov)
  • It can also compete with eukaryotic translation initiation factor (eIF)4G and RNA for eIF4A binding and trap eIF4A in an inactive conformation to inhibit translation initiation via its two highly conserved MA3 domains [3] - [6] . (plos.org)
  • Eukaryotic initiation factor of protein synthesis. (uams.edu)
  • In addition, after transcription, a wide array of RNA-binding proteins interacts with cis -acting elements located mainly in the 3' untranslated region, determining the fate of mRNAs in eukaryotic cells. (frontiersin.org)
  • Most eukaryotic mRNAs are monocistronic, that is, they encode only a single protein. (jove.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)
  • 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)
  • Hi guys, I exported out a promoter list (+/- 2 KB of TSS of all genes) from the UCSC table browser , using knownGene from mm9 (July 2007) which is around 28,330. (biostars.org)
  • It is estimated that over 1 million people will be affected by liver cancer annually by 2025 ( 2 ), and hepatocellular carcinoma (HCC), as the most common form of liver cancer, accounts for approximately 90% of cases ( 3 ). (spandidos-publications.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)
  • Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)
  • IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. (biomedcentral.com)
  • Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2 -dependent manner. (biomedcentral.com)
  • 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)
  • This study aimed to assess the effects of exogenous hydrogen sulfide (H 2 S) on abdominal aorta coarctation (AAC) induced myocardial fibrosis (MF) and autophagy in rats. (kjpp.net)
  • Important roles in the initiation and maintenance of postoperative pain are played by the functional control of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in the rat dorsal horn (DH). (bvsalud.org)
  • Molecular architecture of 40S translation initiation complexes on the hepatitis C virus IRES. (expasy.org)
  • The progression from insulin resistance to type 2 diabetes is caused by the failure of pancreatic β cells to produce sufficient levels of insulin to meet the metabolic demand. (jci.org)
  • We assessed the effect of Chop deletion in multiple mouse models of type 2 diabetes and found that Chop -/- mice had improved glycemic control and expanded β cell mass in all conditions analyzed. (jci.org)
  • Eukaryotic initiation factor 3 (eIF3) is a multiprotein complex that functions during the initiation phase of eukaryotic translation. (wikipedia.org)
  • As initiation proceeds, eIF-2 forms a ternary complex with Met-tRNAi and GTP. (uams.edu)
  • The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
  • In addition, the recurrence rate in the remnant liver, even after R0 resection, has been reported to be up to 80% ( 5 ), and the main treatment is shifted to chemotherapy within 2 years from diagnosis in over 50% of cases diagnosed as early-stage HCC and treated radically with surgery or ablation ( 6 ). (spandidos-publications.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)
  • Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.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)
  • ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma ( NCT03366480 ). (nih.gov)
  • based on a number of pathologic, physiologic, and clinical factors. (msdmanuals.com)
  • These findings suggest that CHOP is a fundamental factor that links protein misfolding in the ER to oxidative stress and apoptosis in β cells under conditions of increased insulin demand. (jci.org)
  • DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)
  • Researchers demonstrated that ENT1 removal from the cell surface was induced by bone marrow stroma cell-secreted factors, and this contributed to cytarabine resistance in AML cells. (haematologica.org)
  • To achieve this, cells of in vitro produced bovine embryos were traced from the 2-cell stage to the blastocyst stage. (bioone.org)
  • On the other hand, ATF-3 is rapidly induced in cells treated with growth stimulators such as serum and growth factors [ 20 ]. (hindawi.com)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • This graph shows the total number of publications written about "Eukaryotic Initiation Factor-2" by people in UAMS Profiles by year, and whether "Eukaryotic Initiation Factor-2" was a major or minor topic of these publications. (uams.edu)
  • Below are the most recent publications written about "Eukaryotic Initiation Factor-2" by people in Profiles over the past ten years. (uams.edu)
  • Seroprevalence of anti-SARS-CoV-2 antibodies in Senegal: a national population-based cross-sectional survey, between October and November 2020. (cdc.gov)
  • Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were screened using three distinct ELISA assays. (cdc.gov)
  • 2 However, resistance mechanisms and targeting strategies can be specific to certain subtypes and mutations. (haematologica.org)
  • Importantly, pro-tumoral perivascular TAMs in breast cancer (BC) are associated with poor prognosis and increased risk of distant metastasis ( Figure 2 ). (lu.se)
  • Under normoxic conditions, prolyl hydroxylases (PHDs) hydroxylate the cite-specific proline residues of HIF-1α in a reaction that uses O 2 as a substrate. (spandidos-publications.com)