Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 40 for “"integrated stress response"”.
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New Roles for the Integrated Stress Response in Cancer and Proteostasis
<p>The integrated stress response (ISR) is a highly conserved pathway that senses diverse stresses and responds by limiting total protein synthesis and redirecting translation to stress response transcripts. The ISR has the potential to modify a broad range of processes in cancer, but the major …
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The effect of alternative splicing on key regulators of the integrated stress response
… (GCN2) is a key regulator of the Integrated stress response that responds to various stress signals, including nutritional deprivation. As a result of high levels of uncharged tRNAs during amino acid depletion, GCN2 phosphorylates serine-51 of the α subunit of eukaryotic initiation …
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Serine Metabolism Leverages the Integrated Stress Response to Direct Stem Cell Fate During Tissue Regeneration
… serine deficiency augments an injury-activated integrated stress response (ISR). Moreover, this response accelerates re-epithelization and rapidly restores the skin's barrier at the wound edge. Altogether, my findings demonstrate that stem cells use serine metabolism and the ISR as regulators of …
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The mechanisms regulating the transcription factor ATF5 and its function in the integrated stress response
… translation during different environmental stresses. Repressed global translation by eIF2 phosphorylation allows for cells to conserve resources and elicit a program of gene expression to alleviate stress-induced injury. Central to this gene expression program is eIF2 phosphorylation …
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A MOLECULE-INHIBITOR OF THE INTEGRATED STRESS RESPONSE REGULATES ACTIVITY OF MAMMALIAN EUKARYOTIC TRANSLATION INITIATION FACTOR 2B
The Integrated Stress Response (ISR) is a conserved eukaryotic translational and transcriptional program implicated in mammalian metabolism, memory and immunity. Although mainly considered to be a protective mechanism, prolonged and severe ISR can result in cell death. The ISR is activated by …
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Genetic analysis of the neuronal integrated stress response in developmental plasticity and organismal physiology of C. elegans
… revealed cell-nonautonomous roles of conserved stress signaling pathways-the Unfolded Protein Response (UPR) and translational control mediated by eIF2[alpha] phosphorylation. While the cell-autonomous functions of these stress-responsive mechanisms in maintaining cellular homeostasis have been …
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Control of Programmed Cell Death by GCN-1
… apoptosis, either physiological (i.e., without stress) or stress-induced, occurs throughout eukaryotic organisms from worms to humans and may have a role in maintaining germline immortality by eliminating compromised germ cells. Therefore the ability to regulate germline apoptosis is intricately …
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The Role of ATF4 in Mediating Skeletal Muscle Function in Response to Acute Contractile Activity
To maintain homeostatic conditions under cellular stress, mitochondria possess the ability to initiate a nuclear retrograde signaling response to counteract the initial stressor and restore optimal organellar functioning. The Integrated Stress Response (ISR) is a newfound mitochondrial quality …
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Towards understanding substrate recruitment by PP1 holophosphatases
… the constitutively expressed PPP1R15B (R15B) or stress inducible PPP1R15A (R15A). These holoenzymes catalyse the dephosphorylation of eIF2α at serine 51, an important signalling event in the integrated stress response pathway, enabling cells to deal with various stresses. The substrate …
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The Heme-Regulated Inhibitor Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics
… heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in response to DHA treatment and represses the synergistic killing of DHA and BH3-mimetics compared to wild-type leukemia. Furthermore, BTdCPU, a …
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Genetic analysis of endoplasmic reticulum homeostasis during stress and infection of Caenorhabditis elegans
Animals experience intrinsic and extrinsic stressors throughout development and adulthood. To maintain cellular and organismal homeostasis, eukaryota and metazoa rely on conserved, integrated stress response pathways. Throughout its life cycle, the free-living nematode Caenorhabditis elegans …
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Screens for non-eukaryotic initiation factor two alpha dependent activation of ATF4 translation
… to signal nutrient availability, cellular stress, and general environmental changes in order to maintain homeostasis, accumulate biomass, and divide. Less is known about how these signaling pathways overlap and interact to produce complex cell phenotypes. Here, I investigate these questions …
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Evolutionary conservation and characterization of the metazoan amino acid response
Signaling pathways that respond to stress and sense nutrient availability are highly conserved throughout eukaryotes. In mammalian cells, these pathways have evolved to regulate immune responses, representing important therapeutic targets. Interestingly, components of these pathways can be found in …
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Roles of PKR in High Grade Serous Ovarian Cancer
… R (PKR; EIF2AK2) is classically described as a stress-activated kinase within the integrated stress response (ISR); however, its role in ovarian cancer metastasis remains poorly defined. In this study, we investigated the functional contribution of PKR to HGSC progression using integrated …
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GCN2 eIF2 Kinase Promotes Prostate Cancer by Maintaining Amino Acid Homeostasis
Activation of the integrated stress response (ISR) contributes to the progression of many cancers, including prostate cancer (PCa). The ISR features a family of protein kinases that phosphorylate the eukaryotic translation initiation factor 2 (eIF2) during different stress conditions, repressing …
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Mitochondrial regulation of CD8+ T cell cytotoxicity
… reactive oxygen species generation and the integrated stress response. Overall, this work uncovers a novel role for mitochondrial translation in CTL cytotoxicity and adds to the growing body of evidence revealing the multifaceted and crucial roles of mitochondria in T cell function.
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Evolutionary conservation and characterization of the metazoan amino acid response
Signaling pathways that respond to stress and sense nutrient availability are highly conserved throughout eukaryotes. In mammalian cells, these pathways have evolved to regulate immune responses, representing important therapeutic targets. Interestingly, components of these pathways can be found in …
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TARGETING METABOLIC PLASTICITY OF GLIOBLASTOMA TUMOR INITIATING CELLS TO RESTORE SENSITIVITY TO LSD1-DIRECTED THERAPY
… TICs ability to restore homeostasis after ER stress or nutrient starvation by hindering a proper Activating transcription factor 4 (ATF4)-dependent integrated stress response (ISR). In line with the GBM intertumor heterogeneity, a cohort of patient-derived TICs displayed resistance toward …
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The role of TREX1 and TREX2 in cellular responses to cisplatin
… mediated by alterations in the DNA damage response (DDR), a complex network of biochemical pathways that maintains genome integrity. Despite extensive research, few DDR inhibitors have been approved for combination with cisplatin. This study aimed to identify novel DDR targets to enhance …
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Interactive Effects of Macronutrients on Obesity and Metabolic Syndrome Development
… was independent of adiposity. In liver, the integrated stress response (ISR) pathway was induced by low protein and fructose, suggesting inhibition of insulin signaling. However, glycogen was increased by low protein in both liver and muscle with concomitant decrease in protein tyrosine …
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