• Childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter leukoencephalopathy (VWM), is a fatal brain disorder caused by mutations in eukaryotic initiation factor 2B (eIF2B). (yeastgenome.org)
  • The eIF2B protein helps regulate overall protein production (synthesis) in the cell by interacting with another protein, eIF2. (medlineplus.gov)
  • Partial loss 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)
  • 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)
  • Mutations affecting the eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, the autosomal recessive childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter disease (VWM). (medlink.com)
  • Vanishing white matter (VWM) is a fatal leukodystrophy that is caused by mutations in genes encoding subunits of eukaryotic translation initiation factor 2B (eIF2B). (knaw.nl)
  • The eukaryotic initiation factor 2B (eIF2B) is a key regulator in protein-regulated signaling pathways and is closely related to the function of the central nervous system. (bvsalud.org)
  • abstract = "Autosomal recessive mutations in eukaryotic initiation factor 2B (eIF2B) cause leukoencephalopathy vanishing white matter with a wide clinical spectrum. (amsterdamumc.org)
  • Activity data for recombinant eIF2B complexes agree closely with those for patient-derived cells with the same mutations. (amsterdamumc.org)
  • Disease is caused by mutations in five genes encoding subunits of the translation initiation factor eIF2B. (biomedcentral.com)
  • Translation initiation factor eIF-2B subunit gamma is a protein that in humans is encoded by the EIF2B3 gene. (wikipedia.org)
  • The N-terminal domain of eukaryotic translation initiation factor 3 subunit 12. (eu.org)
  • Activation of PKR leads to phosphorylation of eukaryotic initiation factor 2 (eIF2) on the α-subunit, which inhibits translation initiation by competing with the guanine nucleotide exchange factor (eIF-2B) for the exchange of GDP for GTP on eIF2. (biomedcentral.com)
  • Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability (PubMed:25329545). (avivasysbio.com)
  • 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)
  • EIF2S1 is one subunit of the translation initiation factor EIF2, which catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. (ptglab.com)
  • Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. (ptglab.com)
  • The eIF2 protein is called an initiation factor because it is involved in starting (initiating) protein synthesis. (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)
  • For example, cells must synthesize protein much faster if they are multiplying than if they are in a resting state. (medlineplus.gov)
  • 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)
  • 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)
  • 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)
  • Each of eFFECTOR's product candidates is designed to act on a single protein that drives the expression of multiple functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival and immune evasion. (tradingview.com)
  • The Human Protein Atlas project can be subdivided into three efforts: Human Tissue Atlas, Cancer Atlas, and Human Cell Atlas. (scientificlabs.ie)
  • PP2A-mediated protein dephosphorylation is involved in a broad range of cellular processes including cell-cycle progression, cytoskeletal dynamics, and growth factor signalling. (eu.org)
  • HEAT repeat domain, found in protein phosphatase 2a and initiation factor eIF4G. (eu.org)
  • MIF4G domain-like, found in eukaryotic initiation factor eIF4G, translation initiation factor eIF-2b epsilon and nuclear cap-binding protein CBP80. (eu.org)
  • The material was named proteolysis-inducing factor (PIF), because of its ability to directly induce protein loss in murine myotubes and isolated muscle preparations, and because this was the name given to an unidentified factor in human serum, which was capable of inducing proteolysis in isolated muscle preparations [ 11 ]. (biomedcentral.com)
  • eIF-2-alpha kinase GCN2;Eukaryotic translation initiation factor 2-alpha kinase 4;GCN2;GCN2 eIF2alpha kinase;GCN2-like protein;general control nonderepressible 2;PVOD2. (avivasysbio.com)
  • Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. (avivasysbio.com)
  • Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). (avivasysbio.com)
  • Comparison of metals in cytotoxicity, free radical generation, and heat shock protein expression in a human bronchial epithelial cell line, BEAS-2B. (cdc.gov)
  • It is caused by mutations in the genes EIF2B1-5 that are involved in initiation and regulation of protein synthesis. (biomedcentral.com)
  • B cell receptor associated protein 31. (gsea-msigdb.org)
  • Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS. (ouhsc.edu)
  • Eukaryotic initiation factor of protein synthesis. (uams.edu)
  • Here we will focus on HMG AT-hook 2 protein (HMGA2), a member of the HMGA family that mediates transforming growth factor beta 1 (TGFB1, commonly known as TGFβ1) signaling 16 . (nature.com)
  • Recent studies indicate that nutrient fluctuations and insulin resistance increase proinsulin synthesis in β cells beyond the capacity for folding of nascent polypeptides within the endoplasmic reticulum (ER) lumen, thereby disrupting ER homeostasis and triggering the unfolded protein response (UPR). (jci.org)
  • Chronic ER stress promotes apoptosis, at least in part through the UPR-induced transcription factor C/EBP homologous protein (CHOP). (jci.org)
  • 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)
  • If a cell experiences stressful conditions, or if there is a sudden demand for more proteins to be made, protein folding can be disrupted. (elifesciences.org)
  • 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)
  • Both mobile and virally encoded kinases get excited about the phosphorylation of tegument protein (5, 11, 12), and serines of tegument proteins HSV-1 VP22 are phosphorylated in contaminated cells (11, 12). (thebiotechdictionary.com)
  • 2004) Mutations causing childhood ataxia with central nervous system hypomyelination reduce eukaryotic initiation factor 2B complex formation and activity. (yeastgenome.org)
  • We performed mutagenesis to introduce changes equivalent to 12 human CACH/VWM mutations in three subunits of the equivalent factor from yeast (Saccharomyces cerevisiae) and analyzed effects on cell growth, translation, and gene expression in response to stresses. (yeastgenome.org)
  • which means both copies of the gene in each cell have mutations. (medlineplus.gov)
  • Here, we have studied the functional effects of selected VWM mutations in EIF2B2-5 by coexpressing mutated and wild-type subunits in human cells. (amsterdamumc.org)
  • genes EIF2B1, 2, 3, 4 and 5) and is the guanine nucleotide-exchange factor (GEF) for eIF2. (amsterdamumc.org)
  • A guanine nucleotide exchange factor that acts to restore EIF-2 to its GTP bound form . (dictionary.net)
  • 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)
  • The motif is conserved in essential proteins throughout the eukaryotic domain of life and also in human viruses, suggesting that the motifs are required for basic cellular function. (eu.org)
  • tRNA má primární strukturu (danou sekvencí nukleotidů), sekundární strukturu (danou interakcemi mezi jednotlivými částmi molekuly tRNA) a terciární strukturu (což je trojrozměrné uspořádání molekuly tRNA) Transfer RNA (tRNA), small molecule in cells that carries amino acids to organelles called ribosomes, where they are linked into proteins. (web.app)
  • The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase), belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. (biomedcentral.com)
  • However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. (nature.com)
  • Although HMG proteins do not possess intrinsic transcriptional activity, they are called architectural transcription factors because they modulate the transcription of their target genes by altering the chromatin structure at the promoter and/or enhancers 15 . (nature.com)
  • Many proteins are made in a compartment within the cell called the endoplasmic reticulum and 'chaperone' proteins help them fold correctly. (elifesciences.org)
  • Cells carefully regulate the levels of chaperone proteins. (elifesciences.org)
  • If there are too few chaperones in the cell, then newly-made proteins may fold incorrectly and interrupt other processes. (elifesciences.org)
  • This leads to an increase in the number of unfolded proteins in the endoplasmic reticulum and so the cell increases the levels of chaperone proteins to cope with this. (elifesciences.org)
  • These proteins can be present in a cell as single molecules (monomers) or as a group of several chaperone molecules (oligomers). (elifesciences.org)
  • Previous research has suggested that the chaperone proteins in oligomers are inactive, but the oligomers may be rapidly broken down into monomers when the cell needs to fold more proteins. (elifesciences.org)
  • Further experiments challenged cells with chemicals that caused the number of unfolded proteins in the cells to increase. (elifesciences.org)
  • However, when the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers that help to deal with the excess numbers of unfolded proteins. (elifesciences.org)
  • Further work is needed to understand how changes in the number of unfolded proteins in cells leads to the formation and disassembly of BiP oligomers. (elifesciences.org)
  • On the other hand, the quantity of HSV-1 tegument proteins UL37 in virions is normally strictly handled despite a 20-fold boost of UL37 in contaminated cells (25). (thebiotechdictionary.com)
  • VP22 relocates to a book subcellular site with another tegument proteins, VP16, in coexpressing cells (7). (thebiotechdictionary.com)
  • In higher eukaryotes the factor consists of three subunits: alpha, beta, and gamma. (uams.edu)
  • Phosphorylation of VP22 coincides using the translocation of VP22 in to the nuclei of HSV-1-contaminated cells (10, 19, 28, 32, 33). (thebiotechdictionary.com)
  • and (v) the increased loss of VP22 tyrosine phosphorylation correlates with minimal VP22 incorporation into virions however, not a decrease in VP22 appearance in virus-infected cells. (thebiotechdictionary.com)
  • The company is also developing Zotatifin, a small molecule designed to inhibit eukaryotic initiation factor 4A (eIF4E), which is in phase 1/2 clinical trial to treat patients with solid tumors. (tradingview.com)
  • Role of eukaryotic translation initiation factor 4E (eIF4E) in cadmium -induced cytotoxicity and cell death. (cdc.gov)
  • Non-treated PC-3 and Calyculin A treated PC-3 cells were subjected to SDS PAGE followed by western blot with 28740-1-AP (Phospho-EIF2S1 (Ser51) antibody) at dilution of 1:2000 incubated 4℃ overnight. (ptglab.com)
  • Integrating known disease genes with physical or biomolecular networks and gene expression data to identify disease-related subnetworks can help us explain many genetic and environmental factors influencing a disease in the context of a smaller number of discrete subnetworks as well as the causes or effects of the disease phenotype. (ijbs.com)
  • Genes down-regulated in comparison of peripheral blood mononuclear cells (PBMC) from TIV influenza vaccinee pre-vaccination versus those at day 3 post-vaccination. (gsea-msigdb.org)
  • Genes down-regulated in CD8A- [GeneID=925] splenic dendritic cells: wildtype versus IFNB1 [GeneID=3456] knockout mice. (gsea-msigdb.org)
  • This two-pronged response involves changes at both the transcriptional level (in the cell nucleus) and the translational level (in the cytoplasm). (elifesciences.org)
  • Venugopal G, Bird JT, Washam CL, Roys H, Bowlin A, Byrum SD, Weinkopff T. In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. (uams.edu)
  • Our data support the concept that chromatin opening during transcriptional initiation involves intermediates with DNA breaks that subsequently require DNA repair mechanisms to ensure genome integrity. (nature.com)
  • Furthermore, we demonstrated the biological relevance of this mechanism of transcriptional initiation within the context of TGFB1 signaling and epithelial-mesenchymal transition (EMT). (nature.com)
  • eFFECTOR's lead product candidate, tomivosertib, is a MNK inhibitor currently being evaluated in KICKSTART, a randomized, double-blind, placebo-controlled Phase 2b trial of tomivosertib in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC). (tradingview.com)
  • Its lead product candidate is Tomivosertib, an oral small-molecule inhibitor of MNK1/2 that is in phase 2b clinical trial for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). (tradingview.com)
  • cyclin dependent kinase inhibitor 2B [So. (gsea-msigdb.org)
  • Activation of PKR also leads to activation of the transcription factor NF-κB, which is responsible for the increased expression of major components of the ubiquitin-proteasome pathway. (biomedcentral.com)
  • activating transcription factor 1 [So. (gsea-msigdb.org)
  • In the eukaryotic cell nucleus, chromatin is the physiological template of all DNA-dependent processes including transcription. (nature.com)
  • ETS transcription factor ELK3 [Source:HG. (gsea-msigdb.org)
  • Dr. Pommier also discovered that the natural compound, ecteinascidin 743 (commercialized as Yondelis) and its analog trabectedin acts by alkylating DNA and killing cancer cells by trapping transcription-coupled nucleotide excision repair (TC-NER) (Takebayashi et al, Nature Med 2001). (cancer.gov)
  • RNA-Seq analysis of primary oligodendrocytes and microglia cells uncovers gene expression signatures associated with activated stress responses and increased post mitotic cellular senescence (PoMiCS) which was confirmed by elevated senescence-associated β-galactosidase activity and SASP gene expression profile. (biomedcentral.com)
  • The antibodies that have been generated in support of the Tissue and Cancer Atlas projects have been tested by immunohistochemistry against hundreds of normal and disease tissues and through the recent efforts of the Human Cell Atlas project, many have been characterized by immunofluorescence to map the human proteome not only at the tissue level but now at the subcellular level. (scientificlabs.ie)
  • METHODS and MATERIALS Cells, trojan, and antibodies. (thebiotechdictionary.com)
  • Activation of GPR4 by acidosis increases endothelial cell adhesion through the cAMP/Epac pathway. (ouhsc.edu)
  • DS cell adhesion molecule [Source:HGNC S. (gsea-msigdb.org)
  • Eukaryotic translation initiation factor 4E is a cellular target for toxicity and death due to exposure to cadmium chloride. (cdc.gov)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • In addition to humoral factors, tumour-derived molecules have also been proposed as mediators of cancer cachexia. (biomedcentral.com)
  • propose that BiP oligomers act as reservoirs to store BiP molecules when they aren't needed by the cell. (elifesciences.org)
  • Scheper GC, Proud CG, van der Knaap MS. Defective translation initiation causes vanishing of cerebral white matter. (medlineplus.gov)
  • Intended Use Human EIF2B1 ELISA Kit allows for the in vitro quantitative determination of EIF2B1 , concentrations in serum, Plasma , tissue homogenates and Cell culture supernates and Other biological fluids. (biobool.com)
  • Here, we used VWM mouse models, patients' tissue, and cell cultures to investigate whether astrocytes or oligodendrocytes are the primary affected cell type. (knaw.nl)
  • Bergmann glia and retinal Müller cells, nonforebrain astrocytes that have not been associated with VWM, were also affected, and involvement of these cells was confirmed in VWM patients. (knaw.nl)
  • In coculture, VWM astrocytes secreted factors that inhibited oligodendrocyte maturation, whereas WT astrocytes allowed normal maturation of VWM oligodendrocytes. (knaw.nl)
  • Guanine Nucleotide Exchange Factors" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ouhsc.edu)
  • This graph shows the total number of publications written about "Guanine Nucleotide Exchange Factors" by people in this website by year, and whether "Guanine Nucleotide Exchange Factors" was a major or minor topic of these publications. (ouhsc.edu)
  • Below are the most recent publications written about "Guanine Nucleotide Exchange Factors" by people in Profiles. (ouhsc.edu)
  • In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. (ptglab.com)
  • Type I Interferons have broad regulatory effects and various subtypes of dendritic cells are influenced by this cytokines. (gsea-msigdb.org)
  • tRNA udgør en undergruppe i gruppen af ikke-kodende RNA. (web.app)
  • RasGRP1 regulates antigen-induced developmental programming by naive CD8 T cells. (ouhsc.edu)
  • Exposure to hot or cold conditions during the critical period of temperature control development causes a plastic change in the ratio between heat- and cold-sensitive cells and can modulate temperature tolerance. (agri.gov.il)
  • Transcriptome data from isolated, primary OLs and microglia cells were explored by in silico pathway analysis and validated by complementary molecular approaches. (biomedcentral.com)
  • Reolysin is a proprietary formulation of oncolytic reovirus that is currently being evaluated in multiple clinical trials due to its ability to selectively replicate in cells harboring an activated RAS pathway. (biomedcentral.com)
  • Reoviruses have been reported to selectively replicate in cancer cells harboring an activated RAS pathway [ 6 ]. (biomedcentral.com)
  • Myelination and homeostatic maintenance of myelin sheaths critically depend on the function of both mature OLs and their progenitor cells (called OPCs or NG2-glia), a process coupled to high energy demand. (biomedcentral.com)
  • In our study we asked question whether the low, constitutive levels of type I Interferons produced under steady state conditions are important for proper function of splenic conventional dendritic cells. (gsea-msigdb.org)
  • Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress. (biomedcentral.com)
  • 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)
  • First and foremost, legislators need to create stable policies and regulatory frameworks to allow industrial scale validation and optimization of microbial cells. (completelyemail.com)