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Peptide Initiation FactorsEukaryotic Initiation Factor-2Eukaryotic Initiation Factor-4EEukaryotic Initiation FactorsEukaryotic Initiation Factor-4GEukaryotic Initiation Factor-4FEukaryotic Initiation Factor-3Eukaryotic Initiation Factor-2BProtein BiosynthesisEukaryotic Initiation Factor-4APeptide Chain Initiation, TranslationaleIF-2 KinaseReticulocytesEukaryotic Initiation Factor-1RibosomesEukaryotic Initiation Factor-5PhosphorylationRNA CapsEukaryotic CellsRNA, Transfer, MetMolecular Sequence DataRNA, MessengerRNA Cap AnalogsTOR Serine-Threonine KinasesProtein KinasesProkaryotic Initiation Factor-2Poly(A)-Binding ProteinsRNA-Binding ProteinsRibosomal Protein S6 KinasesAmino Acid SequenceRabbitsPolyribosomesGuanosine TriphosphatePhosphoproteinsBase SequenceProtein BindingCarrier ProteinsRibosomal Protein S6Codon, InitiatorProteinsRNA Cap-Binding ProteinsProkaryotic Initiation Factor-3Activating Transcription Factor 4Saccharomyces cerevisiaeGuanosine DiphosphateRibosomal Protein S6 Kinases, 70-kDaRibosome Subunits, Small, EukaryoticSirolimusRNA, Transfer, Amino AcylHeLa CellsRNA, Double-StrandedProtein-Serine-Threonine KinasesCell-Free SystemBinding SitesKinetics5' Untranslated RegionsCell LineGuanine Nucleotide Exchange FactorsMutationHeminSignal TransductionMacromolecular SubstancesRNA, TransferSaccharomyces cerevisiae ProteinsProtein Structure, TertiarySequence Homology, Amino AcidProtein Synthesis InhibitorsEndoplasmic ReticulumHemeNucleic Acid ConformationRibosome Subunits, Large, EukaryoticTranscription, GeneticRibosomal ProteinsProtein SubunitsEdeineTranscription Factor CHOPAdaptor Proteins, Signal TransducingPotyvirusCloning, MolecularProkaryotic Initiation FactorsEscherichia coliMolecular WeightMethionineNuclear Cap-Binding Protein ComplexLysineSequence AlignmentLeucineRecombinant ProteinsRNA, ViralTriticumAmino AcidsGene Expression RegulationEnzyme ActivationPicornaviridaeSerineMultiprotein ComplexesBlotting, WesternGuanine NucleotidesElectrophoresis, Polyacrylamide GelPeptide Elongation Factor 2
Translation initiationEIF4GElongationMTORMRNAsAutophagyProteinProteinsInhibitResistanceComplexTranscription factorGeneCellsAlone or in combinationActivitiesFoundRisk factorsTreatmentMRNATranslationalSubunitMTOR inhibitorsTranslation inhibitorEIF4FTumorProtein synthesisDownstreamEIF3DrosophilaApoptosisEvolutionaryMultiple proteinEukaryotesRegulateTranscriptionPI3KPathwayAnalysisStudyCriticalResults
Translation initiation4
  • 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)
  • 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)
  • It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. (wikipedia.org)
  • eIF4A1 is a component of the eIF4F translation initiation complex, along with eIF4E, the 5'-terminal cap binding protein, and eIF4G, the scaffold protein that holds eIF4A and eIF4E together. (wikipedia.org)
EIF4G1
  • 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)
Elongation1
  • BAF60 binds nucleosome-free regions of multiple G box-containing genes, opposing in cis the promoting effect of the photomorphogenic and thermomorphogenic regulator Phytochrome Interacting Factor 4 (PIF4) on hypocotyl elongation. (biomedcentral.com)
MTOR1
  • RAD001 (everolimus), a mammalian target of rapamycin (mTOR) pathway inhibitor in phase II clinical trials in oncology, exerts potent antiproliferative/antitumor activities. (aacrjournals.org)
MRNAs1
Autophagy2
  • For instance, treatment with chloroquine, an autophagy flux inhibitor, overcomes anti-estrogen resistance of MCF-7 cells [ 7 ]. (biomedcentral.com)
  • An inhibitor of autophagy, 3-methyladenine (3-MA), was used to pretreat RAW 264.7 cells. (researchsquare.com)
Protein4
  • Eukaryotic initiation factor 4A-I (also known as eIF4A1 or DDX2A) is a 46 kDa cytosolic protein that, in humans, is encoded by the EIF4A1 gene, which is located on chromosome 17. (wikipedia.org)
  • It is the rate limiting step of protein synthesis, controlled by a myriad of proteins known as the eukaryotic initiation factors, or eIFs. (wikipedia.org)
  • Relative abundance of these factors or their relative individual activities afford eukaryotic cells broad control over the rate of initiation and thus protein synthesis. (wikipedia.org)
  • The structures indicate that Sec61 inhibitors stabilize the plug domain of Sec61 in a closed state, thereby preventing the protein-translocation pore from opening. (biorxiv.org)
Proteins1
  • Some defense proteins such as beta-glucosidase aggregating factor were strongly down regulated and may be regulated directly by opaque2 . (biomedcentral.com)
Inhibit1
  • Anti-epidermal growth factor receptor (EGFR) therapy is an effective way to inhibit proliferation of many cancer types such as non-small cell lung cancer (NSCLC) and colorectal cancer [ 1 ]. (biomedcentral.com)
Resistance2
  • In order to maximize land productivity, the nutritional quality of crops should be one of the factors considered, along with water and nitrogen use efficiency, yield, pest resistance and other determinants of crop productivity [ 2 ]. (biomedcentral.com)
  • Mutations conferring resistance to the inhibitors are clustered at this binding pocket. (biorxiv.org)
Complex2
  • A trimeric peptide initiation factor complex that associates with the 5' MRNA cap structure of RNA ( RNA CAPS ) and plays an essential role in MRNA TRANSLATION . (nih.gov)
  • Cryo-EM structures of the human Sec61 complex inhibited by various small-molecule inhibitors. (biorxiv.org)
Transcription factor2
  • The transcription of eIF4A1 is driven by the transcription factor MYC. (wikipedia.org)
  • The bZIP ELONGATED HYPOCOTYL 5 (HY5) transcription factor is another major regulator of thermo- and photomorphogenesis. (biomedcentral.com)
Gene2
  • These include the upregulation of immune gene Csf1 (colony stimulating factor 1) in primary sensory neurons. (elifesciences.org)
  • The cdc25 gene product is a tyrosine phosphatase that acts as an initiator of M-phase in eukaryotic cell cycles by activating p34 cdc2 . (biologists.com)
Cells6
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • Of these steps, initiation is the one for which cells have the most control. (wikipedia.org)
  • Improved methods and pharmaceutical compositions are provided herein for mobilizing hematopoietic progenitor cells from bone marrow into peripheral blood, comprising the administration of an effective amount of an inhibitor of GTPases, such as Rac1 and Rac2 alone or in combination. (justia.com)
  • Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
  • 2012 ). In vitro , flavopiridol suppresses the interaction between leukocytes and endothelial cells in the model of murine hepatitis, which is a crucial step in the initiation of inflammation (Schmerwitz et al. (researchsquare.com)
Alone or in combination1
  • However, EGFR-tyrosine kinase inhibitor (TKI) alone or in combination therapy with paclitaxel or docetaxel had been used for breast cancer patients in clinical trials, but both therapies failed [ 2 ]. (biomedcentral.com)
Activities1
  • 2011 ). In addition to antitumor activities, CDK inhibitors (CDKi) show prominent anti-inflammatory effects (Leitch et al. (researchsquare.com)
Found1
Risk factors3
  • Although various risk factors for PEP have been reported, the prediction of PEP remains controversial. (bvsalud.org)
  • Risk factors for TRGOO were also explored. (bvsalud.org)
  • 2018 ). Corneal trauma after agricultural injury and contact lens usage have been recognized as the predominant risk factors (Mahmoudi et al. (researchsquare.com)
Treatment2
  • Letrozole (Femara) is an aromatase inhibitor used for treatment of postmenopausal women with hormone-dependent breast cancers. (aacrjournals.org)
  • The concept of synthetic lethality (SL) holds great promise for the treatment of human cancers, best exemplified by the now widespread use of PARP inhibitors in BRCA mutant cancers. (nature.com)
MRNA5
  • We recently demonstrated that mammalian NAT1 mRNA, encoded by EIF4G2, uses GUG as its only translation initiation codon. (nih.gov)
  • Poly(A)-binding protein (PABP) is a key player in mRNA circularization and translation initiation of polyadenylated mRNAs. (microbiologyresearch.org)
  • N6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). (biomedcentral.com)
  • N6-methyladenosine (m6A) was first discovered in eukaryotic messenger RNA (mRNA) [ 2 , 3 ] and viral nuclear RNA [ 4 , 5 ] in the 1970s and has been identified as one of the most common and abundant RNA modifications. (biomedcentral.com)
  • We uncovered deficits in insulin secretion, partly due to reduced mitochondrial oxygen consumption rate, glucose-stimulated Ca 2+ flux, and reduced insulin content associated with loss of eIF4E, the mRNA 5′ cap-binding protein of the initiation complex and binding partner of eIF4G1. (diabetesjournals.org)
Translational2
  • A new translational regulator with homology to eukaryotic translation initiation factor 4G. (nih.gov)
  • Altogether these data demonstrate an essential role for the translational factor eIF4G1 on glucose homeostasis and β-cell function. (diabetesjournals.org)
Subunit2
  • eIF4E is a subunit of the eIF4F protein initiation complex and required for its recruitment. (biomedcentral.com)
  • The eukaryotic 80S ribosome is composed of a 60S large subunit and a 40S small subunit. (lookformedical.com)
MTOR inhibitors2
  • [ 6 ] Whether BCL-2 overexpression will emerge as a determinant of clinical resistance to rapamycin therapy remains to be seen in ongoing clinical trials of mTOR inhibitors for cancer. (medscape.com)
  • We recently reported that mTOR inhibitors induce apoptosis via ER stress and the extrinsic pathway upon acute inhibition of the eIF4F complex in colon cancer cells and xenografts, while mutant BRAF600E leads to therapeutic resistance via ERK-mediated Mcl-1 stabilization. (oncotarget.com)
Translation inhibitor1
  • The PABP-specific translation inhibitor PABP-interacting protein 2 (Paip2) interferes with the DENV 3′UTR-PABP interaction, and in vitro translation of DENV reporter RNAs in baby hamster kidney cell extracts is inhibited by Paip2 in a dose-dependent manner. (microbiologyresearch.org)
EIF4F2
  • It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. (wikipedia.org)
  • These findings highlight the importance of highly efficacious direct inhibitors of eIF4E and eIF4F assembly, which could potentially target a wide spectrum of tumours containing differing mutations that effect these pathways and which confer chemo-resistance. (biomedcentral.com)
Tumor3
  • 4. [Role of eukaryotic translation initiation factor 4G in tumor]. (nih.gov)
  • This evaluation included the determination of peak and trough RAD001 levels in tumor tissue and blood, examination in tumor tissue of phosphorylation of downstream mTOR targets (ribosomal protein S6, eukaryotic translation initiation factor 4G), and detailed analysis of changes in gene expression over time. (medscape.com)
  • Tumor suppressor APC is lost in 85% of CRCs, leading to β-catenin stabilization, activation of Wnt targets such as c-Myc (Myc) and cyclin D1 and cancer initiation, which cooperates with hyperactivated RAS/RAF/ERK, and PI3K/AKT/mTOR signaling in cancer progression [ 2 , 3 ]. (oncotarget.com)
Protein synthesis3
  • Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors. (nih.gov)
  • Relative abundance of these factors or their relative individual activities afford eukaryotic cells broad control over the rate of initiation and thus protein synthesis. (wikipedia.org)
  • It is an antineoplastic and antitrypanosomal agent and is used in research as an inhibitor of protein synthesis. (lookformedical.com)
Downstream2
  • In all species, the GUG codon fulfilled the reported requirements for non-AUG initiation: an optimal Kozak motif and a downstream hairpin structure. (nih.gov)
  • Reduced protein level of a requisite scaffolding protein of the initiation complex, eIF4G1, downstream of nutrients and insulin signaling is associated with diabetes in humans and mice. (diabetesjournals.org)
EIF31
  • DDX3 specifically enhanced the association of the cap-binding complex (CBC) with uORF-containing mRNAs and facilitated recruitment of the eukaryotic initiation factor 3 (eIF3). (aacrjournals.org)
Drosophila1
  • We found that NAT1 orthologs in Drosophila melanogaster and Halocynthia roretzi also use non-AUG start codons, demonstrating evolutionary conservation of the noncanonical translation initiation. (nih.gov)
Apoptosis1
  • This combination led to marked induction of ER stress and ATF4/CHOP, followed by DR5- and BAX-dependent apoptosis, but unexpectedly with maintained or even increased levels of prosurvival factors such as p-AKT, p-4E-BP1, Mcl-1, and eiF4E targets c-Myc and Bcl-xL. (oncotarget.com)
Evolutionary2
  • TrypTag is a transformative resource, important for hypothesis generation for both eukaryotic evolutionary molecular cell biology and fundamental parasite cell biology. (nature.com)
  • T . brucei is an early-branching eukaryote (Fig. 1a ), giving enormous insight into eukaryote evolutionary cell biology and losses or gains in organelle complexity since the last eukaryotic common ancestor. (nature.com)
Multiple protein1
Eukaryotes2
  • We provide clues to function and define lineage-specific organelle adaptations for parasitism, mapping the ultraconserved cellular architecture of eukaryotes, including the first comprehensive 'cartographic' analysis of the eukaryotic flagellum, which is vital for morphogenesis and pathology. (nature.com)
  • Moreover, the flagellum is also a widely conserved organelle in eukaryotes and a defining feature of the last eukaryotic common ancestor 9 , but not yet analysed by genome-wide protein localization mapping using microscopy. (nature.com)
Regulate1
Transcription1
  • The transcription of eIF4A1 is driven by the transcription factor MYC. (wikipedia.org)
PI3K1
  • Growth factor receptor tyrosine kinases (RTKs) recruit PI3K to the membrane. (medscape.com)
Pathway1
  • In this study, we demonstrated that several other translation inhibitors also activate ER stress and the extrinsic apoptotic pathway. (oncotarget.com)
Analysis1
  • Multivariable regression analysis showed that factors significantly associated with increased risk of readmission included age, length of stay of the index admission, medical specialty of admission other than neurology/neurosurgery, and level of hospital, after adjustment for sex, Charlson comorbidity index score, and primary discharge diagnosis (ischemic/hemorrhagic stroke versus others). (nih.gov)
Study2
  • In this study, we identified NAT1 orthologs from chicken, Xenopus, and zebrafish and found that in all species, the GUG codon also serves as the initiation codon. (nih.gov)
  • The aim of this study was to analyze the CRP gene allelic variations in the Turkish adult risk factor (TARF) study and relate them with serum CRP levels as well as MetS and its components. (nih.gov)
Critical1
  • Site-directed mutagenesis showed that nucleotides at positions -3 and +4 are critical for the GUG-mediated translation initiation in vitro. (nih.gov)
Results1
  • The results showed that the surface area increased by a factor of 3.3, 2.0 and 1.8 referred to the parent CNFs after the treatment with KOH, K(2)CO(3) and KHCO(3), respectively. (nih.gov)