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Kinetic Dissection of Translation Initiation in Prokaryotes.Filonava, Liudmila 18 June 2013 (has links)
No description available.
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The mechanism of protein synthesis inhibition by the P56 family of viral stress inducible proteins /Hui, Daniel Jason. January 2005 (has links)
Thesis (Ph. D.)--Case Western Reserve University, 2005. / [School of Medicine Molecular Virology Program. Includes bibliographical references. Available online via OhioLINK's ETD Center.
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Characterization of GTP and aminoacyl-tRNA binding to eukaryotic initiation factor 2 and elongation factor 1Kinzy, Terri Goss January 1991 (has links)
No description available.
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The Reciprocal Regulation of Nitric Oxide Synthase and Alpha-subunit of Eukaryotic Initiation Factor 2 Post Ultraviolet B IrradiationLu, Wei January 2010 (has links)
No description available.
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Mechanisms of Adaptation to Deformylase InhibitorsZorzet, Anna January 2010 (has links)
Antibiotic resistance is a growing problem on a global scale. Increasing numbers of bacteria resistant toward one or multiple antibiotics could return us to the high mortality rates for infectious diseases of the pre-antibiotic era. The need for development of new classes of antibiotics is great as is increased understanding of the mechanisms underlying the development of antibiotic resistance. We have investigated the emergence of resistance to peptide deformylase inhibitors, a new class of antibiotics that target bacterial protein synthesis. The fitness of resistant mutants as well as their propensity to acquire secondary compensatory mutations was assessed in order to gain some insight into the potential clinical risk of resistance development. Most of this work was done in the bacterium Salmonella typhimurium, due to the availability of excellent genetic tools to study these phenomena. In addition, we have studied the bacterium Staphylococcus aureus as peptide deformylase inhibitors have been shown to have the greatest effect on Gram-positive organisms. In the course of this work we also examined the mechanistic aspects of translation initiation. Using a cell-free in vitro translation system we studied the effects of various components on translation initiation. These results have been combined with results obtained from resistant and compensated bacterial strains in vivo to gain new insights into the mechanisms of translation initiation.
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Function of Nck-1 adaptor protein as modulator of elF2alpha phosphorylation by specific elF2alpha kinases and PKR activityCardin, Eric. January 2008 (has links)
Phosphorylation of the alpha-subunit of the eukaryotic initiation factor 2 (eIF2alpha) on Serine 51 (Ser51) is an early event associated with downregulation of protein synthesis at the level of translation and constitutes a potent mechanism to overcome various stress conditions. In mammals, four eIF2alpha-kinases PERK, PKR, HRI and GCN2, activated following specific stresses, have been involved in this process. Our laboratory has previously demonstrated that the adaptor protein Nck, composed only of Src homology domains and classically implicated in cell signaling by activated plasma membrane receptor tyrosine kinases, modulates translation through its interaction with the beta-subunit of the eukaryotic initiation factor 2 (eIF2beta). Moreover, we reported that Nck-1 overexpression antagonizes the inhibition of translation in endoplasmic reticulum stress condition and prevents the PERK-mediated phosphorylation of the alpha-subunit of eIF2 on Ser51. In this thesis, I demonstrate that the adaptor protein Nck-1 modulates eIF2alpha-kinase-mediated eIF2alphaSer51 phosphorylation in a specific manner. More particularly, I show that Nck-1 overexpression reduces eIF2alpha phosphorylation in conditions activating PKR or HRI as described previously for PERK. In contrast, I observe that overexpression of Nck-1 in mammalian cells fails to attenuate eIF2alphaSer51 phosphorylation in response to amino acid starvation, a stress condition activating GCN2. I further confirm this observation by showing that Nck-1 fails to alter eIF2alphaSer51 phosphorylation in Saccharomyces cerevisiae, for which the sole eIF2alpha-kinase is GCN2. In addition, I report that Nck-1 reduces PKR activation in response to dsRNA. I also find that Nck-1 reduces dsRNA-induced activation of p38 MAPK, a PKR-downstream substrate, and cell death. Finally, I show that Nck-1 interacts exclusively with the inactivated form of PKR in a Src homology domain independent manner. All together these data uncover the existence of a novel mechanism regulating phosphorylation of eIF2alphaSer51 under various stress conditions and identifies Nck-1 as a modulator of the tumor suppressor and antiviral protein kinase PKR.
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Upstream open reading frames differentially regulate genespecific translation in the integrated stress responseYoung, Sara Kathryn 13 May 2016 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Gene expression is a highly coordinated process that relies upon appropriate
regulation of translation for protein homeostasis. Regulation of protein synthesis largely
occurs at the initiation step in which the translational start site is selected by ribosomes
and associated initiating factors. In addition to the coding sequences (CDS) for protein
products, short upstream open reading frames (uORFs) located in the 5’-leader of
mRNAs are selected for translation initiation. While uORFs are largely considered to be
inhibitory to translation at the downstream CDS, uORFs can also promote initiation of
CDS translation in response to environmental stresses. Multiple transcripts associated
with stress adaptation are preferentially translated through uORF-mediated mechanisms
during activation of the Integrated Stress Response (ISR). In the ISR, phosphorylation
of α subunit of the translation initiation factor eIF2α (eIF2α~P) during environmental
stresses results in a global reduction in protein synthesis that functions to conserve
energy and nutrient resources and facilitate reprogramming of gene expression.
Many key regulators of the ISR network are subject to preferential translation in
the response to eIF2α-P. These preferentially translated genes include the pro-apoptotic
transcriptional activator Chop that modifies gene expression programs, feedback
regulator Gadd34 that targets the catalytic subunit of protein phosphatase 1 to
dephosphorylate eIF2α~P, and glutamyl-prolyl tRNA synthetase Eprs that increases the
charged tRNA pool and primes the cell for resumption of protein synthesis after stress
remediation. Ribosome bypass of at least one inhibitory uORF is a common theme
between Chop, Gadd34, and Eprs, which allows for their regulated expression in
response to cellular stress. However, different features encoded within the uORFs of the Chop, Gadd34, and Eprs mRNAs provide for regulation of their inhibitory functions,
illustrating the complexities of uORF-mediated regulation of gene-specific translation.
Importantly, preferentially translated ISR targets can also be transcriptionally regulated
in response to cellular stress and misregulation of transcriptional or translational
expression of Gadd34 can elicit maladaptive cell responses that contribute to disease.
These mechanisms of translation control are conserved throughout species,
emphasizing the importance of translation control in appropriate gene expression and
the maintenance of protein homeostasis and health in diverse cellular conditions.
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Function of Nck-1 adaptor protein as modulator of elF2alpha phosphorylation by specific elF2alpha kinases and PKR activityCardin, Eric. January 2008 (has links)
No description available.
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