Дисертації з теми "Eukaryotic initiation factor eIF4GI"
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Li, Qiyu. "Eukaryotic translation initiation factor eIF4AIII is functionally distinct from eIF4AI and eIF4AII." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0035/MQ64391.pdf.
Повний текст джерелаLi, Qiyu 1972. "Eukaryotic translation initiation factor eIF4AIII is functionally distinct from eIF4AI AND eIF4AII." Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30687.
Повний текст джерелаShahbazian, David. "Eukaryotic initiation factor 4B (eIF4B) : regulation by signaling pathways and its role in translation." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115902.
Повний текст джерелаSignal transduction regulates multiple cellular processes including mitogenesis, differentiation, apoptosis, chemotaxis etc. Signaling pathways also regulate ribosomal biogenesis to coordinate mitogenic cues, nutrient and energy availability with the translational capacity of the cells. Mounting evidence links PI3K-Akt-mTOR and Ras-MAPK cascades to the translational control. In this thesis, I show that PI3K/mTOR and MAP kinase cascades converge to phosphorylate eIF4B on Ser422. This phosphorylation results in an increased interaction with eIF3, an essential factor bridging between eIF4F and the small ribosomal subunit. Physiological significance of eIF4B phosphorylation on Ser422 has been demonstrated by the stimulatory effect of eIF4B Ser422Asp phosphomimetic mutant on cap-dependent translation. Taken together, this represents a new paradigm of translational control mechanism regulated by signaling crosstalk. The function of eIF4B in vitro is well characterized but its in vivoeffects are disputed in literature. To address this I established HeLa cell line stably expressing shRNA targeting eIF4B. eIF4B silencing inhibits proliferation rates and anchorage-independent growth. Expression of luciferase reporter gene containing 5' terminal oligopyrimidine tract (TOP) is selectively repressed in eIF4B-silenced cells and can be rescued by exogenous eIF4B regardless of Ser422 phosphorylation status. Moreover, the de novo synthesis rates of endogenous ribosomal proteins in serum starved cultures recapitulate the luciferase reporter assay data. Utilizing polysomal analysis, I was able to show more significant inhibition of translation initiation in serum starved eIF4B-silenced cells. Our attempt to discover novel eIF4B-interacting proteins by Mass Spectrometry approach led to the identification of nucleolar RNA helicase DDX21. Confocal microscopy has shown partial co-localization of tagged eIF4B and DDX21 in nucleolar periphery. Pulse chase experiments metabolically labeling rRNA show an attenuated 28S rRNA production and concomitant accumulation of 36S intermediates in eIF4B-silenced cells. Since ribosomal biogenesis is highly coordinated process and requires strict stoichiometry maintenance of ribosomal components the observed inhibition of rRNA processing could be consequential to the decreased ribosomal protein expression. However, given the fact that eIF4B is associated with the nucleolar pre-ribosomal particle complexes its direct effect on rRNA processing cannot be ruled out. Regulation of ribosomal biogenesis by translation initiation factor may represent an important control mechanism allowing cells to co-ordinate these two processes.
Combe, Jonathan P. "The isolation and functional analysis of the eukaryotic translation initiation factor eIF4E from tobacco." Thesis, University of Leicester, 1998. http://hdl.handle.net/2381/29777.
Повний текст джерелаRuud, Kelley Astrid. "Identification and characterization of a novel cap-binding protein from Arabidopsis thaliana and of the wheat eukaryotic initiation factor eIF4G /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
Повний текст джерелаJones, Grant D. "Discovery, Phylogenetic Analysis, and Functional Characterization of a Unique Family of Eukaryotic Translation Initiation Factor 4E, eIF4E, From Amphidinium carterae, a Marine Dinoflagellate." Thesis, University of Maryland, Baltimore, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10118645.
Повний текст джерелаThis study investigates the eIF4E family members in Dinoflagellates. Dinoflagellates are eukaryotic algae with large genomes and a minimal role for transcriptional regulation. All mRNA in dinoflagellates is trans -spliced with a 22-nucleotide 5'-spliced-leader sequence bearing a multi-methylated cap. Like other eukaryotes, dinoflagellates encode multiple eIF4E family members that are anticipated to fulfill a range of functions. Three distinct and novel clades of eIF4E have been recognized in dinoflagellates that are separate from the three metazoan classes of eIF4E. The dinoflagellate Amphidinium carterae encodes eight eIF4E family members while Karlodinium veneficum encodes fifteen eIF4E family members. I assayed six of these family members from A. carterae for expression levels, m7GTP binding, yeast knockout complementation and affinity for three mRNA cap analogs using surface plasmon resonance (SPR). Transcripts of each are expressed through a diel cycle, but only eIF4E-1 family members and eIF4E-2a are expressed at the level of protein. Recombinant eIF4E-1 family members and eIF4E-3a, but not eIF4E-2a, are able to bind to m 7GTP-agarose beads. Of the clade 1 eIF4Es, only eIF4E-1a and -1d1 complement a S. cerevisiae strain conditionally deficient in functional eIF4E, consistent with their function as translation initiation factors. However, only eIF4E-1a can be recovered from A. carterae extracts by m7GTP affinity binding. Using SPR analysis, the affinity of A. carterae eIF4E-1a for m7GTP is lower than that of murine eIF4E-1A. By the same analysis, A. carterae eIF4E-1a has a higher affinity for m7GpppG than m7GTP. In addition, K. veneficum eIF4E-1a1 displays many of the same characteristics as A. carterae eIF4E-1a. Four eIF4E-1 and one eIF4E-2 family members from K. veneficum were characterized for m7GTP binding capacity, only the eIF4E-1 family members can be pulled down with m7GTP. Three eIF4E family members were tested for their ability to interact with a putative eIF4E-interacting protein, although none interacted. Overall, the eIF4E-1a sub-clade emerges with characteristics consistent with the role of a prototypical translation initiation factor. These initial analyses will allow for a better understanding of specific translational control of gene expression through mRNA recruitment in the unique dinoflagellate lineage.
Metz, Anneke Maria. "Function of the wheat eukaryotic initiation factors eIF(ISO)4G and eIF4B in translation /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
Повний текст джерелаGreen, Simon Richard. "Molecular analysis of eukaryotic initiation factor 2#alpha#." Thesis, University of Kent, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330170.
Повний текст джерелаBottari, Nicolas. "Putative role of eukaryotic initiation factor 4AIII in the nucleus." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=78325.
Повний текст джерелаFennell, Clare. "Characterisation of the eukaryotic initiation factor 2alpha kinases of Plasmodium falciparum." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/527/.
Повний текст джерелаAndrieu, Claudia. "Etude des mécanismes d'action d'Hsp 27 responsables de l'évolution androgéno-indépendante des cancers de la prostate : mise en évidence de nouvelles stratégies thérapeutiques." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4007.
Повний текст джерелаProstate cancer (PC) has become a real public health issue in industrialized countries, mainly due to patients' relapse by castration-resistant (CR) disease after androgen ablation. One strategy to improve current therapies in advanced PC involves targeting genes that are activated by androgen withdrawal, either to delay or prevent the emergence of the CR phenotype. Hsp27 is over-expressed in this cancer and has been shown to play a cytoprotective role leading to treatments resistance. This protein is now considered as promising therapeutic target. Rocchi, P. et al. developed and patented a second generation antisens oligonucleotides (ASO) targeting Hsp27 that has been licensed (OGX-427) and phase II clinical trials are currently in process in PC in Canada and USA. My PhD project focused on the study of Hsp27 action mechanisms involved in CRPC progression. The present study aims to improve pharmacological safety of OGX-427 and to identify new therapeutic targets specific of CRPC cells. The results of my PhD have shown that during cell stress induced by hormone- and/or chemotherapy, Hsp27 interacts with eukaryotic translation initiation factor eIF4E and protects it from degradation by the ubiquitin/proteasome pathway. This maintains protein synthesis and leads to cell survival, partly involved in the cytoprotection mediated by Hsp27. Our work therefore concerned the characterization of the interaction site between Hsp27 and eIF4E in order to identify potential inhibitors of this interaction that could delay CRPC progression
Carroll, Matthew 1978. "Characterizing the role of eukaryotic elongation factor 2 and eukaryotic initiation factor 4E binding protein in rapamycin-sensitive signaling in Aplysia." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80235.
Повний текст джерелаPhosphorylation of the eukaryotic initiation factor 4E binding protein (4EBP) increases the availability of the mRNA cap-binding eukaryotic initiation factor 4E and is also rapamycin-sensitive. We found that 4EBP phosphorylation at threonine 37/46 was stimulated in a rapamycin-sensitive manner in Aplysia neuronal processes, although it is possible that other 4EBP phosphorylation sites are also rapamycin-sensitive.
Livingstone, Mark. "A nuclear role for the eukaryotic translation initiation factor 4E-binding proteins." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97024.
Повний текст джерелаLa régulation de la traduction des ARN messagers (ARNm) est d'une importance cruciale afin de contrôler quelles protéines sont produites en réponseaux signaux intra- et extracellulaires. La collection de protéines fonctionnelles quien résulte détermine quels processus physiologiques seront effectués par la cellule. Conséquemment, la dérégulation du contrôle traductionnel est fortement impliquée dans plusieurs pathologies, incluant le cancer, ceci dû au fait que les cellules ne répondent pas de manière appropriée aux stimuli qu'elles reçoivent. Une voie de signalisation impliquée dans la croissance et la prolifération cellulaire qui est souvent dérégulée dans les cancers, la voie de la cible mammifère de la rapamycine (mTOR), et qui intègre la disponibilité en acides aminés, facteurs de croissance et énergie avec la traduction des ARNm, est une cible pharmacologique préférentielle. Parmi les effecteurs de la voie mTOR, on retrouve les protéines s'associant au facteur d'initiation de la traduction eIF4E, les 4E-BP, qui lorsqu'elles sont phosphorylées relâchent la protéine liant la coiffe5' des ARNm, eIF4E, promouvant ainsi la traduction des ARNm encodant des protéines impliquées dans la croissance et la prolifération. En contraste avec les résultats de fractionnement subcellulaires reportés précédemment dans la littérature suggérant que 4E-BP1 est une protéine exclusivement cytoplasmique, nous montrons ici, par essais immunologique, que cette protéine est également v résidente du noyau des cellules mammifères où elle séquestre eIF4E suivant l'inhibition de mTOR. Cette accumulation nucléaire de eIF4E est un biomarqueur de choix que nous avons utilisé comme lecture du niveau d'activité de la voie mTOR lors d'un criblage chimio-génétique entrepris dans le but de trouver de nouveaux inhibiteurs de la voie mTOR. Cette découverte d'un complexe nucléaire eIF4E :4E-BP1 à ouvert la porte à une possible fonction des 4E-BP dans certains processus nucléaires. Les évidences en faveur et en opposition àun tel rôle nucléaire spécifique des 4E-BPs sont évaluées et la fonction nucléaire des 4E-BPs est testée expérimentalement.
Murphey, Roberta Jean. "Synthesis of deoxyhypusine in eukaryotic initiation factor 4D in rat hepatoma cells." Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184691.
Повний текст джерелаQuenouille-Lederer, Julie. "Bases génétiques et fonctionnelles de la durabilité des résistances polygéniques au virus Y de la pomme de terre (PVY) chez le piment (Capsicum annuum)." Thesis, Avignon, 2013. http://www.theses.fr/2013AVIG0650/document.
Повний текст джерелаGenetic resistances provide an efficient control of crop diseases but are limited by pathogen adaptation.In pepper, the durability of the pvr23 allele, conferring resistance to Potato virus Y (PVY), was demonstrated todepend on the plant genetic background. The aim of my PhD thesis was to characterize the host genetic factorsaffecting the durability of the major resistance gene pvr23 and to answer to the following question s: (i) What istheir action on the evolution of the viral population? (ii) Is there identity between the QTLs (quantitative traitloci) controlling the partial resistance and the QTLs affecting the durability of pvr23? (iii) Are these genetic factorswidespread among the genetic resources of pepper? Various experiments including resistance testing,experimental evolution and competition between various PVY variants, enabled to show that the genetic factorsaffecting the durability of pvr23 acted in: (i) decreasing the viral accumulation, (ii) decreasing the probability ofacquisition of resistance breaking (RB) mutations by PVY and (iii) slowing down the selection of RB variants. QTLdetection and mapping of genetic factors affecting the frequency of pvr23 RB showed that four loci actingadditively and in epistatic interactions explained together 70% of the variance of pvr23 breakdown frequency.Comparative mapping between these QTLs and QTLs affecting partial resistance showed that three of the fourQTLs controlling the frequency of pvr23 RB are also involved in quantitative resistance, suggesting that QTLs forquantitative resistance have a pleiotropic effect on the durability of the major resistance gene. Analysis of acollection of 20 pepper accessions, carrying pvr23 or pvr24 (allele closely related to pvr23) in various geneticbackgrounds, showed that genetic backgrounds favorable to the durability of the pvr2-mediated resistance arewidespread in the genetic resources of pepper. These results highlight that the durability of a major resistancegene can be strongly increased when associated with genetic factors decreasing the pathogen multiplication.Moreover, the frequency of a major gene RB is a highly heritable trait and QTLs detection for this trait isachievable. The direct selection for such QTLs opens new prospects to preserve the durability of major resistancegenes used by breeders
Ali, I. K. "The role of eukaryotic initiation factor 4F in translation initiation by linear scanning and internal ribosome binding." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.595445.
Повний текст джерелаKinzy, Terri Goss. "Characterization of GTP and aminoacyl-tRNA binding to eukaryotic initiation factor 2 and elongation factor 1." Case Western Reserve University School of Graduate Studies / OhioLINK, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1055276346.
Повний текст джерелаAbdulkarim, Baroj. "The eukaryotic translation initiation factor 2, a hero turned villain in β cells". Doctoral thesis, Universite Libre de Bruxelles, 2017. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/251713.
Повний текст джерелаDoctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
Hoose, Alex. "Cyclic peptide inhibitors of the eukaryotic translation initiation factor 4E and 4G interaction." Thesis, University of Southampton, 2016. https://eprints.soton.ac.uk/403847/.
Повний текст джерелаGentz, Petra Monika. "Towards understanding the mechanism of dimerisation of Saccharomyces cerevisiae eukaryotic translation initiation factor 5A." Thesis, Rhodes University, 2008. http://eprints.ru.ac.za/1161/.
Повний текст джерелаFleming, Keiran Paul. "Liquid crystal NMR : application to a bacterial adhesin and a eukaryotic translation initiation factor." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409641.
Повний текст джерелаLazaris-Karatzas, Anthoula. "Eukaryotic translation initiation factor 4E : its characterization as a proto-oncogene and mechanism of action." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39569.
Повний текст джерелаTo further elucidate the mechanism of elF-4E transformation we determined Ras activity in elF-4E transformed REFs. We detected an activation of Ras in eIF-4E overexpressing cells as compared to parental REFs. In addition, overexpression of GAP (GTPase activating-protein), a negative regulator of Ras, suppressed the transformation of REFs by elF-4E.
In summary we have established an important link between Ras, which plays a key role in cellular signal transduction, and elF-4E which is a critical component of the translation machinery.
Charlton, Jane Laura. "Understanding the biomolecular interactions involved in dimerisation of the Saccharomyces cerevisiae eukaryotic translation initiation factor 5A." Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1004118.
Повний текст джерелаKazemi, Shirin. "The role of eukaryotic initiation factor 2 alpha phosphorylation pathway in translational control and virus-mediated oncongenesis /." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103165.
Повний текст джерелаZyryanova, Alisa. "A molecule-inhibitor of the integrated stress response regulates activity of mammalian eukaryotic translation initiation factor 2B." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284208.
Повний текст джерелаSun, Yingjie. "Single-molecule studies of the eukaryotic translation initiation factor 4A: helicase activity, conformational dynamics and function regulation." Thesis, Boston University, 2013. https://hdl.handle.net/2144/11060.
Повний текст джерелаThe PI3K/Akt/mTOR pathway regulates several cellular functions, including cellular proliferation, growth, and survival. The PI3K/Akt/mTOR pathway converges on the eukaryotic translation initiation factor 4F (eIF4F), making it an attractive molecular target for anti-cancer therapies. As a subunit of eIF4F, eIF4A is known to facilitate binding and scanning of the ribosome by unwinding secondary structures in the 5' untranslated region (UTR) of mRNAs. However, the molecular mechanisms of eIF4A activity have remained elusive. Single-molecule Fluorescence Resonance Energy Transfer (sm-FRET) can probe structural changes and interactions of biological systems in real time, which cannot be observed using bulk techniques. First we directly observe and quantify the helicase activity of eIF4A in the presence of the ancillary RNA-binding factor eIF4H using sm-FRET. We show that eIF4H can significantly enhance the helicase activity of eIF4A by strongly binding both to loop structures within the RNA substrate as well as to eIF4A. Electrophoretic mobility shift assay (EMSA) shows that eIF4H binds to the amino-terminal domain (NTD) but not to the carboxyterminal domain (CTD) of eIF4A. In the presence of ATP, the eIF4A/eIF4H complex exhibits rapid and repetitive cycles of unwinding and re-annealing. ATP titration assays suggest that this process consumes a single ATP molecule per cycle. Second, we directly probe the conformational dynamics of eIF4A, in real time, using smFRET. We demonstrate that the eIF4A in the presence of eIF4H can repetitively unwind the RNA hairpin substrate by transitioning between an "open" and a "closed" conformation using the energy from ATP hydrolysis. Upon binding of an RNA hairpin and ATP, which is mediated by eIF4H, eIF4A adopts a closed conformation; after ATP hydrolysis, eIF4A returns to the open conformation and the RNA duplex is completely unwound. Then the eIF4A releases the RNA and the hairpin is quickly reformed. Third, we find that RNA aptamer and the small molecule hippuristanol can inhibit the binding to the RNA substrate or the helicase activity of the eIF4A/eIF4H complex respectively. The RNA aptamer can directly compete with an RNA hairpin for binding to both eIF4A and eIF4H. Hippuristanol inhibits helicase activity by blocking the conformational change of eIF4A.
Avison, Matthew B. "The role of phosphorylation in the interaction between eukaryotic initiation factor elF4E and 4E-BP1 in rat adipocytes." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263829.
Повний текст джерелаElsby, Rachel Jane. "The Alpha Subunit of Eukaryotic Initiation Factor 2B Is Requisite for EIF2-Mediated Transitional Suppression of Vesicular Stomatitis Virus." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/33.
Повний текст джерелаLong, Ezhou. "Proliferation and apoptosis of bovine mammary epithelial cells : roles of eukaryotic translation initiation factor 4E and Escherichia coli mastitis." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37766.
Повний текст джерелаBecause of its unknown sequence, bovine eIF-4E cDNA was then cloned in the second study. Its coding region consists of 651 nucleotides which encode 217 amino acids (AAs). Bovine eIF-4E cDNA shares 94%, 89% and 94% homology with those of human, mouse and rabbit, respectively. Differences in protein sequences between bovine and human, mouse and rabbit eIF-4E are 2, 4, and 3 AAs, respectively. Furthermore, expression of eIF-4E in bovine mammary tissues at different physiological periods was investigated by Northern blot analysis, using the cloned cDNA as the probe. eIF-4E was not detectable at prepubertal period and expressed at a very low level at the third estrous cycle. In the lactating mammary tissues, eIF-4E was highly expressed. Differential expression of eIF-4E in bovine mammary gland at distinct physiological stages indicates its potential involvement in mammary development.
Cell proliferation and apoptosis were also studied in the Escherichia coli (E. coli)-infected bovine mammary glands in the last study. Both proliferation and apoptosis increased in the mastitic tissue, as determined by immunohistological assays. Compared to the controls, expression of the pro-apoptotic proteins, Bax and interleukin-1beta converting enzyme (ICE), increased at 24 h and 72 h post-infection, whereas expression of the anti-apoptotic protein Bcl-2 decreased only at 24 h post-infusion. Induction of extracellular matrix (ECM)-degrading enzymes, including matrix metal loproteinase-9 (MMP-9), stromelysin-1 (SL-1) and urokinase-type plasminogen activator (uPA), was also observed in the mastitic tissue. Therefore, apoptosis may be mediated through pathways involving the actions of Bcl-2, Bax and ICE, and may partially be accounted by ECM breakdown.
Taken together, our study has demonstrated the effect of eIF-4E on bovine mammary cell proliferation. In addition, its involvement in bovine mammary gland development has been suggested. Finally, increased mammary cell apoptosis and proliferation during E. coli-induced mastitis has been revealed, in association with altered expression of apoptosis-related genes and ECM-degrading enzymes. Understanding the regulation of mammary cell proliferation and death may eventually lead to improvement of milk production.
Lu, Wei. "The Reciprocal Regulation of Nitric Oxide Synthase and Alpha-subunit of Eukaryotic Initiation Factor 2 Post Ultraviolet B Irradiation." Ohio University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1289006333.
Повний текст джерелаTalje, Lama. "Structural basis for the recruitment of the SerThr kinase Mnk1 by the scaffolding proteins DAP5 and elF4G." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111548.
Повний текст джерелаLiu, He. "Eukaryotic Initiation Factor 2-associated glycoprotein P67 inhibits the tumorigenicity of Alveolar Rhabdomyosarcoma (ARMS) and involves its differentiation and migration." Kent State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1564585690280704.
Повний текст джерелаGatsukovich, Yulia. "Characterization of Eukaryotic Translation Initiation Factor 5A-2 (eIF5A-2) in Arabidopsis thaliana: Effects of Wounding and Pathogen Attack." Thesis, Waterloo, Ont. : University of Waterloo, 2004. http://etd.uwaterloo.ca/etd/ygatsuko2004.pdf.
Повний текст джерела"A thesis presented to the University of Waterloo in fulfillment of the thesis requirement for the degree of Master of Science in Biology." Includes bibliographical references.
Eshaque, Bithi. "Characterization of Eukaryotic Translation Initiation Factor 5A isoforms (eIF-5A1 & eIF-5A2) using human cell lines as a model system." Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/1218.
Повний текст джерелаThere are two isoforms of eIF-5A in the human genome which have designated eIF-5A1 and eIF-5A2. The objective of the present study was to gain an increased understanding of the roles of eIF-5A1 and eIF-5A2 during apoptosis and cell proliferation using human cell lines as a model system. Apoptosis was induced by treating the cells with Actinomycin D or sodium nitroprusside (SNP), which initiate programmed cell death by different mechanisms. It was observed for both normal and cancer cells that eIF-5A1 protein is up-regulated during apoptosis induced by Actinomycin D or SNP, whereas eIF-5A1 mRNA is constitutively expressed and does not change in abundance during this treatment. The up regulation of eIF-5A1 protein levels in the absence of a corresponding up-regulation in eIF-5A1 mRNA suggests that eIF-5A1 may be post-transcriptionally regulated. Moreover, eIF-5A1 protein up-regulation was stronger in normal cells than in cancer cells. By contrast, eIF-5A2 protein was below detection levels during apoptosis in both normal and cancer cells, although the corresponding transcript was detectable by semi-quantitative RT-PCR. This is attributable to inefficient translation of eIF-5A2 mRNA.
The effects of eIF-5A1 and eIF-5A2 on cell proliferation were examined by modulating the levels of serum in cultures of UACC-1598 cells, which are ovarian cancer cells that express high levels of both isoforms of eIF-5A. Serum starvation, which induces cell cycle arrest and ensuing apoptosis, followed by the re-addition of serum had no effect on the transcript levels of either eIF-5A1 or eIF-5A2. However, eIF-5A1 and eIF-5A2 proteins were both up-regulated within 24 hours of the initiation of serum starvation, and this coincided temporally with the onset of apoptosis as measured by TUNEL and a subsequent decline in viable cells.
The data indicate that eIF-5A1 and eIF-5A2 are both post-transcriptionally regulated and that they have functionally redundant roles in apoptosis.
Muaddi, Hala. "Phosphorylation of eukaryotic initiation factor 2-alpha at serine 51 is an important determinant of cell survival and adaptation to glucose deficiency." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:8881/R/?func=dbin-jump-full&object_id=92253.
Повний текст джерелаRUSSO, ARIANNA. "Increasing Eukaryotic Initiation Factor (eIF6) gene dosage stimulates global translation and induces a transcriptional and metabolic rewiring that blocks Programmed Cell Death." Doctoral thesis, Università del Piemonte Orientale, 2018. http://hdl.handle.net/11579/97190.
Повний текст джерелаHui, Daniel Jason. "The Mechanism of Protein Synthesis Inhibition by the P56 Family of Viral Stress Inducible Proteins." Connect to text online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1104848977.
Повний текст джерелаHoang, Xuan Chien [Verfasser], and Wilhelm [Akademischer Betreuer] Schäfer. "The role of posttranslational hypusination of the eukaryotic translation initiation factor 5A in Zea mays and Fusarium graminearum / Xuan Chien Hoang ; Betreuer: Wilhelm Schäfer." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2017. http://d-nb.info/1130787044/34.
Повний текст джерелаLee, Yun-Young. "Translational regulation of growth arrest and DNA damage-inducible gene GADD34 via its 5' untranslated region upstream open reading frame during eukaryotic initiation factor 2 alpha phosphorylation." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/17442.
Повний текст джерелаMajumdar, Avijit. "Regulation of the activation and activity of the extra-cellular signal regulated kinases 1 & 2 MAP kinase pathway by eukaryotic initiation factor 2 associated glycoprotein p67." [Kent, Ohio] : Kent State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1209000031.
Повний текст джерелаTitle from PDF t.p. (viewed Jan. 26, 2010). Advisor: Bansidhar Datta. Keywords: p67, ERK1, ERK2, oncogenic KRasV12, tumor suppressor. Includes bibliographical references (p. 143-160).
Gradi, Alessandra. "Translational control in eukaryotes : discovery of a novel human eukaryotic translation initiation factor and its role in the shutoff of host cell protein synthesis following entero- and rhinovirus infections." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36809.
Повний текст джерелаIn contrast to cellular mRNAs, entero- and rhinovirus RNAs do not possess a cap structure, and their translation is mediated by ribosome binding to an internal ribosome entry site present within the 5' untranslated region. The cleavage of eIF4G induced by the viral protease 2A is thought to be responsible for the shutoff of host protein synthesis in entero- and rhinovirus-infected cells. Nonetheless, in virus-infected cells, a lack of correlation between eIF4GI cleavage and inhibition of host translation is observed. eIF4GII, like eIF4GI, is also cleaved upon viral infection. Here, I present data showing that the kinetics of cleavage of eIF4GII perfectly coincide with the inhibition of cellular protein synthesis observed after entero- and rhinovirus infection. Thus, proteolysis of both eIF4GI and eIF4GII appears to be required for the shutoff of host protein synthesis after entero- and rhinovirus infections.
Cardin, Eric. "Function of Nck-1 adaptor protein as modulator of elF2alpha phosphorylation by specific elF2alpha kinases and PKR activity." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111905.
Повний текст джерелаLarsson, Ola. "Transcriptome studies of cell-fate and aging /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-296-9/.
Повний текст джерелаMurphy, Patrick. "Characterisation of critical interactions between translation factors eIF2 and eIF2B." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-critical-interactions-between-translation-factors-eif2-and-eif2b(9138d7c8-34b1-4489-8048-a2ac45ef8533).html.
Повний текст джерелаIll-Raga, Gerard. "Study of the pathophysiological role of nitric oxide and nitrative stress in brain: translational effects on the cleavage of the amyloid precursor protein in Alzheimer's disease and post-translational effects on fibrinogen in brain ischemia." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/31907.
Повний текст джерелаL’òxid nítric (NO) és un neurotransmissor involucrat en processos de memòria. Actualment, l’única cascada de senyalització fisiològica controlada per NO consisteix en l’activació de la guanilat ciclasa. En aquesta tesi, en proposem una d’alternativa que inclou la fosforilació de eIF2a per la Heme-regulated eukaryotic initiation factor-2a kinase (HRI). Hem mostrat com l’enzim BACE1, una proteïna clau en la malaltia d’Alzheimer (AD), és controlat per aquesta nova cascada de senyalització, que podria estar involucrada en la fisiologia de l’aprenentatge i la memòria. També hem estudiat com un factor d’estrès extern, l’ Herpes Simplex Virus 1, pot pertorbar aquesta cascada donant lloc a increments patològics en BACE1 i pèptid ß-amiloide (Aß). L’Aß agrega formant fibril·les que generen radicals lliures. Aquests reaccionen químicament amb NO produint peroxinitrit, que contribueix a la progressió de l’AD. Pel fet que l’NO esdevé tòxic quan és produït en un entorn pro-oxidant, hem estudiat també l’impacte que el peroxinitrit té en l’ictus.
Souza, Maria Sigride Thomé de. ""Leucoencefalopatia com substância branca evanescente: estudo clínico e de neuroimagem"." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-17042006-094726/.
Повний текст джерелаLeukoencephalopathy with vanishing white matter is an inherited disorder caused by mutation in one of five subunits of eIF2B gene. Age of onset varies from prenatal to adulthood and manifestations are commonly triggered by trauma or infection. Symptoms are variable and include cerebellar ataxia and spasticity, with relative sparing of cognitive function. Magnetic resonance imaging (MRI) findings are typically characterized by widespread white matter abnormality. We studied 10 patients, with sudden or slowly progressive symptoms starting between 1-12 years of age. Ataxia and spasticity were present in all patients, and cognitive functions were relatively preserved. MRI studies demonstrated diffuse white matter abnormalities which, combined with clinical findings, allow diagnosis
Sanséau, Doriane. "Étude du récepteur CD95 et de son rôle pro-inflammatoire dans le lupus." Thesis, Rennes 1, 2015. http://www.theses.fr/2015REN1S134.
Повний текст джерелаThe death ligand CD95L, mainly expressed by immune cells, contributes to the elimination ofinfected and transformed cells. In pathological contexts, CD95L can be expressed by others cell types such as endothelial cells.CD95L can be cleaved by metalloproteases to generate a soluble CD95L (cl-CD95L) failing to trigger the apoptotic signaling pathwaybutinducing non-pro-apoptotic signaling pathways. cl-CD95L promotes inflammation in chronic inflammatory disorders such as systemic lupus erythematosus (SLE) and increases risks of metastatic dissemination in breast cancer patients. In SLE patients, we established that high amounts of cl-CD95L fuels inflammation by promoting endothelial transmigration of activated Th17 cells. This CD95-drivencell migration requires PLCγ1 recruitment by CD95 and the subsequentimplementation of the calcium signal. To identify in an exhaustive fashion, all molecular partners of CD95, a global proteomic analysis was undertaken. This TAP-Tag approach highlighted a strong association between the translational machinery and CD95. This analysis was confirmed by a two-hybrid approach revealingthat the translation initiation factor eIF4A1 directly interactedwith CD95.In breast cancer cells, we established that eIF4A1 was instrumental in the translation of certain genes such as Akt contributing to the implementation of the CD95-mediated PI3K signaling pathway and cell migration. In this study, we identifiedthe CD95 domaininvolved in the induction of the non-apoptotic signaling pathway. This domain was named CID for “calcium inducing domain”.Moreover, wegenerated a therapeutic molecule consisting of theCID fused to the cationic cell-penetrating HIV TAT domain. TAT-CID prevented the accumulation of Th17 cells in inflamed organs of lupus-prone mice and could turn out to be an original therapeutic molecule to alleviate clinical symptoms in SLE patients
Rapone, Roberta. "Essential cytoplasmic role(s) of the histone lysine methyltransferase Setdb1 in post-transcriptional regulation of gene expression." Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/RAPONE_Roberta_va.pdf.
Повний текст джерелаSetdb1 is a “histone” lysine methyltransferase (KMT) belonging to the SUV39 family that methylates lysine 9 of histone H3 (H3K9), one of the major epigenetic machineries mainly involved in gene repression. Notably, Setdb1 establishes mono-, di- and tri-methylation of H3K9. Setdb1, or Eset in mice, is essential for the survival, the pluripotency and the self-renewal of mouse embryonic stem cells (mESCs); Eset knockout is lethal at the peri-implantation stage at 3.5 dpc in mice. Setdb1 is also required for the differentiation of many progenitor cell types: spermatogenesis, neurogenesis, chondrocyte differentiation and skeletal muscle differentiation. Moreover, Setdb1 has been associated with several diseases: it is amplified in melanoma and lung cancer and it is dysregulated in liver, prostate, colorectal and breast cancers, Huntington disease and schizophrenia.Remarkably, beyond histones, Setdb1 methylates many non-histone substrates, such as UBF, p53, AKT, Tat and ING2 proteins. Although Setdb1 has been always associated with its nuclear role, it turns out that Setdb1 is the only H3K9 KMT to have also a cytoplasmic localization, in several cell types, including mESCs, mouse embryonic fibroblasts (MEFs) and HeLa cells. However, the function of Setdb1 in the cytoplasm remains totally unknown. To investigate Setdb1 cytoplasmic role, we have used mouse embryonic stem cells (mESCs), in which Setdb1 is essential. Our results show that cytoplasmic Setdb1 is crucial for the survival of mESCs: indeed, the number of apoptotic cells increases after the loss of cytoplasmic Setdb1. We found that cytoplasmic Setdb1 affects newly protein synthesis in mESCs. We further show that cytoplasmic Setdb1 interacts with mESCs-specific protein Trim71 (also called Lin41) and with the initiation translation factor eIF3c in mESCs. Finally, we reported that Setdb1 and Trim71 together co-regulate mRNA stability and translation. Our current data unravel the essential cytoplasmic function of Setdb1, for long time considered exclusively an “histone” lysine methyltransferase, and provide new insights into the post-transcriptional regulation of gene expression mediated by a fundamental epigenetic regulator
Chu, Chia-Ying. "Molecular Mechanism of RNA-Mediated Gene Silencing in Human Cells: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/388.
Повний текст джерелаBark, Abed El Rahim. "Conditional inactivation of EIF2B5 gene in oligodendrocytes or astrocytes cell lineages in adult mice." Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/BARK_Abed_El_Rahim_1_complete_20191218.pdf.
Повний текст джерелаVanishing white matter disease (VWMD) or childhood ataxia with central nervous system hypomyelination (CACH) is an autosomal recessive demyelinating disorder with wide phenotypic heterogeneity caused by autosomal recessive mutations in the genes encoding the five subunits of the translation-initiation factor eIF2B. It causes cerebral white matter devastations and rarefactions with an atypical morphology of astrocytes and a “foamy” morphology of oligodendrocytes. Several animal models were developed to understand the pathophysiology of the disease and to investigate therapeutic strategies. In our studies, we established two new mouse models. In the first, we targeted the eif2b5 gene in oligodendrocytes in the tamoxifen inducible form of Cre (CreERT2) expressed in the locus of the oligodendrocyte-specific proteolipid protein (PLP) that allows precisely timed gene deletion in adult oligodendrocytes (Plp-Cre-ERT2/Eif2b5fl/fl). (i) In adult female mice, we observed after nine weeks of induction a significant loss of weight and acute paralysis; (ii) Behavioral tests, showed a deficiency in motor coordination and locomotor activity, and a loss of muscular strength; (iii) At the histological level, we observed a decrease of olig2/CC1 mature oligodendrocytes with persistence and even an increase in the pool of immature cells. On the other hand, an increase of number of GFAP+ astrocytes and Iba1+ microglia has been observed in cortex with an activated aspect of both cell types in addition to a neuronal loss; (iv) Electronic microscopy showed a non-significant but obvious tendency to decrease in the number of myelinated axons; (v) RNAseq analysis on cells sorted (MACS) from brains of adult mice showed the activation of pathways related to chronic stress, especially in the immature (O4+) oligodendrocytes and the reprogramming of the expression of genes favoring the maintaining of the immature cells and the activation of neuroinflammation pathways when going into the symptomatic phase. In the second model, we targeted the eif2b5 gene in astrocytes using the same system with the Cre expressed in the locus of the Glutamate-Aspartate Transporter (Glast) protein that allows precisely timed gene deletion in adult astrocytes (Glast-Cre-ERT2/Eif2b5fl/fl) which resulted in two distinct phenotypes related to the presence or not of a copy of the Glast locus in the resulting mice (Glast-Cre-ERT2+/-/Eif2b5fl/fl where one copy of Glast exists and Glast-Cre-ERT2-/-/Eif2b5fl/fl where no copy of Glast exists). (i) In the Glast-Cre-ERT2+/-/Eif2b5fl/fl TMX treated female mice, no weight loss nor paraplegia were observed; (ii) At the histological level, we observed an increase of number of GFAP+ astrocytes and Iba1+ microglia with an activated aspect of both cell types while no oligodendrocyte nor neuronal loss were seen in contrast to the Glast-Cre-ERT2-/-/Eif2b5fl/fl where (iii) significant loss of weight and paraplegia were observed at six weeks after induction; (iv) an increase of number of GFAP+ astrocytes and Iba1+ microglia has been observed with an activated aspect of both cell types in addition to mature oligodendrocyte and neuronal loss. This whole work underlines the susceptibility of oligodendrocyte cells, particularly the immature ones, to chronic ER stress induced by EIF2B deficit. The astrocytes require the association of many factors in order to cause acute neurologic distress. They might be more involved in the developmental and chronic phase