• 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)
  • AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. (senescence.info)
  • Pelletier, J. Abstract: Levels of eukaryotic initiation factor 4E (eIF4E) are frequently elevated in human cancers and in some instances have been associated with poor prognosis and outcome. (edu.lb)
  • Translation of vascular endothelial growth factor (VEGF), matrix metallopeptidase 9 (MMP9) and cyclin D1 mRNAs, which encode products associated with the metastatic phenotype, is inhibited upon eIF4E suppression. (edu.lb)
  • This inhibition is associated with the increased phosphorylation of eukaryotic initiation factor (eIF2) α, increased association of eIF4E with the inhibitory eIF4E-binding protein (4E-BP1), and specific cleavages of eIF4B and eIF2α. (gla.ac.uk)
  • Sepsis altered the distribution of eukaryotic initiation factor 4E (eIF4E) in the gastrocnemius by increasing the amount associated with 4E-BP1 (inactive complex) and decreasing the amount bound to eIF4G (active complex). (psu.edu)
  • These pathways involve mTOR-dependent activation of the 70 kDa ribosomal protein S6 kinase (p70S6K) as well as the inactivation of the repressor of mRNA translation, eukaryotic initiation element 4E (eIF4E) binding protein (4EBP) [1,2]. (researchensemble.com)
  • The latter overrides the repressing activity of 4E-BP1 on the eukaryotic initiation factor 4E (eIF4E), resulting in enhanced translation of a subset of growth promoting genes (Hay and Sonenberg 2004). (ebrary.net)
  • Translational control of mRNAs is mediated in part by eukaryotic initiation factor 4E (eIF4E). (ecu.edu)
  • 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)
  • a metabolic energy sensor or cellular fuel gauge), tuberous sclerosis complex (TSC), and mammalian target of rapamycin (mTOR). (biomedcentral.com)
  • Control of the last three of these is linked to mTOR (mammalian target of rapamycin). (silverchair.com)
  • Here we utilize transgenic and allograft breast cancer models to demonstrate that increased mammalian target of rapamycin (mTOR) signalling can be a significant contributor to breast cancer progression in vivo. (edu.lb)
  • Furthermore, the phosphorylation of ribosomal protein S6 and mammalian target of rapamycin (mTOR) was also decreased in the gastrocnemius from septic rats. (psu.edu)
  • Hence, the decreased constitutive protein synthesis observed in fast-twitch skeletal muscle in response to peritonitis is mediated by a TNF-dependent mechanism affecting mTOR regulation of translation initiation. (psu.edu)
  • Background The serine-threonine protein kinase mammalian target of rapamycin (mTOR), which is definitely inhibited from the immunosuppressant drug rapamycin regulates several intracellular pathways in response to numerous extracellular signals, nutrient availability, energy status of the cell and stress. (researchensemble.com)
  • Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). (ksdb.org)
  • AKT phosphorylation and inactivation of TSC2 results in increased levels of the GTP-bound (active) form of Rheb1, which in turn promotes the phosphorylation and activation of mTOR, also known as the mammalian target of rapamycin (Manning and Cantley 2003). (ebrary.net)
  • Subsequently, mTOR phosphorylates key eukaryotic translation regulators, including p70-S6 kinase (p70S6K) and the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (Hay and Sonenberg 2004). (ebrary.net)
  • 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)
  • Phosphorylation of Eukaryotic Initiation Factor 2 by Heme-Regulated Inhibitor Kinase-Related Protein Kinases in Schizosaccharomyces pombe Is Important for Resistance to Environmental Stresses. (en-academic.com)
  • TcK2 knockout cells lost phosphorylation of eukaryotic initiation factor 3 and cyclic AMP responsive-like element, recognized to promote growth, likely explaining both decreased proliferation and augmented differentiation. (qxmd.com)
  • CK2 (proteins kinase CK2) may phosphorylate eIF2 (eukaryotic translation initiation aspect 2) phosphorylation of eIF2 also pointed to Ser2 being a preferred site for CK2 phosphorylation. (bioinf.org)
  • The current presence of three lysine blocks and phosphorylation sites for proteins kinase CK2 and PKC (proteins kinase C) are quality from the N-terminal area of mammalian eIF2 [21]. (bioinf.org)
  • The websites phosphorylated on mammalian eIF2 have already been mapped at Ser2, Ser67 (both targeted by CK2), Ser13 (targeted by PKC) and Ser218 [targeted by PKA (proteins kinase A)] [21]. (bioinf.org)
  • Preliminary studies for the practical outcomes of mammalian eIF2 phosphorylation for proteins synthesis showed it Formoterol supplier did not influence the power of eIF2 to create the ternary complicated with GTP and Met-tRNAiMet [33]. (bioinf.org)
  • Hydrolysis of eIF2-GTP occurs after the Met-tRNAi has recognized the AUG. This reaction is catalyzed by eIF5 (or eIF5B) and is thought to cause dissociation of all other initiation factors and allow joining of the large 60S ribosomal subunit. (reactome.org)
  • A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo. (reactome.org)
  • EIF2 - (Eukaryotic Initiation Factor 2) is an eukaryotic initiation factor. (en-academic.com)
  • The TcK2 protein kinase of Trypanosoma cruzi, the causative agent of Chagas disease, is structurally similar to the human kinase PERK, which phosphorylates the initiation factor eIF2α, and in turn, inhibits translation initiation. (qxmd.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)
  • Previously, we found that eukaryotic initiation factor (eIF) 4A interacts with cyclin dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. (aber.ac.uk)
  • Jeffrey, I. W. , Bushell, M. , Tilleray, V. J. , Morley, S. and Clemens, M. J. (2002) Inhibition of protein synthesis in apoptosis: differential requirements by the tumor necrosis factor alpha family and a DNA-damaging agent for caspases and the double-stranded RNA-dependent protein kinase. (gla.ac.uk)
  • We have previously shown that absence of TcK2 kinase impairs parasite proliferation within mammalian cells, positioning it as a potential target for treatment of Chagas disease. (qxmd.com)
  • The class I PI3Ks are activated by growth factor tyrosine kinase receptors (class IA), such as EGFR, or by G protein coupled receptors (GPCRs) (class IB). (ebrary.net)
  • eIF4A is a highly conserved RNA-stimulated ATPase and helicase involved in the initiation of mRNA translation. (aber.ac.uk)
  • Two mammalian eIF4A paralogs, eIF4A1 and eIF4A2, have been assumed to be redundant because of their high homology, and the difference in their functions has been poorly understood. (biorxiv.org)
  • Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. (uni-frankfurt.de)
  • Protein synthesis in mammalian cells is regulated through alterations in the states of phosphorylation of eukaryotic initiation factors and elongation factors (eIFs and eEFs respectively) and of other regulatory proteins. (silverchair.com)
  • AKT prevents cell death by inactivating proapoptotic factors including BAD, procaspase-9 and Forkhead transcription factor family proteins (FOXOs), activates transcription factors that upregulate antiapoptotic genes, including NF-kB, inactivates p53 through Mdm2, and phosphorylates the cell cycle inhibitors p21 CIP1/WAF1 and p27 KIP1 , thus increasing cell proliferation (Hennessy et al. (ebrary.net)
  • Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. (senescence.info)
  • Exposure of mammalian cells to agents that induce apoptosis results in a rapid and substantial inhibition of protein synthesis. (gla.ac.uk)
  • In MCF-7 breast cancer cells, tumor necrosis factor α (TNFα) and TNF-related apoptosis-inducing ligand inhibit overall translation by a mechanism that requires caspase (but not necessarily caspase-3) activity. (gla.ac.uk)
  • Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. (cusabio.com)
  • Function of eukaryotic initiation factor 5 in the formation of an 80 S ribosomal polypeptide chain initiation complex. (reactome.org)
  • Eukaryotic translation initiation factor 3 subunit J (eIF3j) is a protein that in humans is encoded by the EIF3J gene. (wikipedia.org)
  • Overview of all the structural information available in the PDB for UniProt: O75822 (Human Eukaryotic translation initiation factor 3 subunit J (EIF3J)) at the PDBe-KB. (wikipedia.org)
  • and elongation factor eEF2, which mediates the translocation step of elongation. (silverchair.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)
  • It is apparent from previous studies with yeast and mammalian cells that hypusine-modified eIF-5A facilitates the translation of a subset of mRNAs mediating cell division. (cornell.edu)
  • Oryza sativa Japonica Group eukaryotic initiation factor 4A-1-like (LOC4341966), transcript variant X1, mRNA. (genscript.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)
  • Features of signaling through the mammalian target of rapamycin complex 1 pathway via the tuberous sclerosis 1/tuberous sclerosis 2 complex. (medlink.com)
  • 2006). In turn AKT plays a key role in the transmission of pro-proliferative and transforming pathways initiated by EGFR and multiple growth factor receptors, as well as by oncogenic active PI3K mutants (Luo et al. (ebrary.net)
  • Purification and characterization of homogeneous initiation factor M2A from rabbit reticulocytes. (reactome.org)
  • I. Purification and characterization of seven initiation factors. (reactome.org)
  • Isolation and characterization of senescence-induced cDNAs encoding deoxyhypusine synthase and eucaryotic translation initiation factor 5A from tomato. (cornell.edu)
  • 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)
  • CB1 and CB2 have been cloned and characterized from mammalian tissues, the main difference between them being their tissue expression pattern [ 6 ]. (oncotarget.com)
  • In addition, ife-1 spermatocytes prematurely accumulated pro-apoptotic CED-4, homolog to mammalian Apaf-1, during spermatogenesis. (ecu.edu)
  • The infective forms of T cruzi are contained in the feces of the insect vectors and gain entry into its mammalian hosts through contamination. (medscape.com)
  • As with other parasites that infect both mammalian and insect hosts, the life cycle of T cruzi is complex (see image below). (medscape.com)
  • Whether these cell development effects will also be exerted on mammalian cells hasn't however been explored. (bioinf.org)
  • Encodes eukaryotic translation initiation factor 5A (EIF-5A).In mammalian cells it functions as a shuttle protein that translocates mRNA from the nucleus to cytoplasmic ribosomes. (or.jp)
  • As epimastigotes (depicted in the first image below) move to the hindgut, they differentiate into metacyclic trypomastigotes (depicted in the second image below), which are nondividing forms resistant to mammalian complement that have the capacity to infect mammalian cells. (medscape.com)
  • Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.com)
  • both E2F1 and c-Myc are stimulating factors of H19 expression, and the H19 lncRNA functions as a downstream effector of c-Myc and E2F1 in tumor development and progression [ 11 ]. (jcancer.org)
  • Moreover, infusion of the inflammatory cytokine tumor necrosis factor α (TNF-α) into naive rats produces a comparable decrement. (psu.edu)
  • IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. (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)
  • Therefore, the purpose of the present study was to determine whether inhibition of TNF action under in vivo conditions could prevent the sepsis-induced decrease in translation initiation observed in the postabsorptive state. (psu.edu)
  • comfirmed the existence of m7G inside mammalian mRNA for the first time and pioneered the invention of a new type of epigenetic sequencing method (m7G-seq) to reveal the distribution sites of m7G modifications [ 11 ], which laid the foundation for the related research of m7G subsequent modification. (beds.ac.uk)
  • Exposure to a variety of growth factors has also been shown to increase HIF-1 activity in normoxic and hypoxic conditions. (spandidos-publications.com)
  • Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. (senescence.info)
  • For several years, researchers have focused on the role of insulin-like growth factor (IGF)-1 as a primary signaling molecule that mediates skeletal-muscle growth in response to resistance exercise, given that resistance exercise stimulates the secretion of IGF-1. (humankinetics.com)
  • The ability of TNF BP to prevent the sepsis-induced alterations in translation initiation was independent of change in plasma insulin and proportional to the insulinlike growth factor I content in blood and muscle but was associated with a reduction in plasma corticosterone. (psu.edu)
  • This mechanism of transmission contrasts with that of the two subspecies of African trypanosomes that cause human disease, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense , which are transmitted via the saliva of their vectors, and with the mechanism by which the nonpathogenic trypanosome found in the Americas, Trypanosoma rangeli , is transmitted to its mammalian hosts. (medscape.com)
  • T cruzi can also be transmitted when mammalian hosts ingest infected insects, and this mechanism of transmission may play a major role in maintaining the sylvatic cycle. (medscape.com)
  • Long non-coding RNAs (lncRNAs) are non-coding RNAs longer than 200 nucleotides that function as regulatory factors in many human diseases, including cancer. (jcancer.org)
  • In fungus, deletion from the lysine blocks compromises cell development, Formoterol supplier which factors to a significant role because of this structural feature [7]. (bioinf.org)
  • In 1994, through application of broad range molecular cell signal transduction and possibly eukaryotic transcrip- amplification and DNA sequencing, the causative agent tion. (cdc.gov)
  • Eukaryotic translation initiation factor (eIF) 4A - a DEAD-box RNA-binding protein - plays an essential role in translation initiation. (biorxiv.org)
  • 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)