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 21 for “"Integrated Stress Response (ISR)"”.
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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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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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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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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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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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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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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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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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The eIF2 phosphatase: characterization and modulation
… network that controls protein production in response to cellular requisites. Thereby, protein synthesis is induced or attenuated depending on the particular cellular conditions. One of the mechanisms to control protein synthesis is the phosphorylation of eIF2, which triggers the so-called …
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Respiratory chain deficiency alters cellular proteostasis and triggers Alzheimer’s disease-like tau alterations
… dysfunction leads to AD-relevant retrograde responses. Retrograde responses maintain cellular homeostasis by adapting nuclear gene expression and cytosolic signaling pathways to changes in mitochondrial function. AD mitochondrial dysfunction likely initiates numerous retrograde responses, yet …
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The Role of Specific Integrase Strand Transfer Inhibitors (INSTIs) in the Alteration of Oligodendrocyte Maturation and Myelination in Hand
… initiation factor 2α(eIF2α) throughthe cellular integrated stress response (ISR). Finally, in vivo,mice receiving EVG/COBI failed to remyelinate the corpus callosum during the three week recovery period following demyelination, after cuprizone treatment. Although EVG/COBI treatment by itself did …
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Investigating The link Between High-Risk Protein Kinase R-Like Endoplasmic Reticulum Kinase (PERK) Haplotypes, Periodontal Inflammation and Depression in People With HIV (PWH) on Antiretroviral Therapy ( ART)
… suppression. The endoplasmic reticulum (ER) stress sensor, protein kinase R–like endoplasmic reticulum kinase (PERK), encoded by EIF2AK3, is a crucial part of the integrated stress response (ISR) that regulates cellular adaptation to viral and inflammatory stimuli. Genetic variations in …
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The Role of tRNA methyltransferases in Cancer
… as pivotal regulators of cellular homeostasis, stress adapta- tion, and disease, particularly within the context of cancer. Among these, tRNA modifications play a crucial role in maintaining translational fidelity and supporting cancer cell survival under adverse conditions. This thesis explores …
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Transcriptional Regulation of the Metabolic Response to Therapy in Leukemia
<p>Cancer cells are under constant stress due to their uncontrolled growth, oncogenic signaling, and the metabolic insufficiencies of their microenvironments. Under various stresses, cells activate the integrated stress response (ISR), a transcriptional program to restore cellular homeostasis. …
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Investigating the anti-leukaemic effect of tamoxifen in the myeloproliferative neoplasms
… with specific molecular pathways such as integrated stress response (ISR), proinflammatory signalling, mitochondrial activity and proteotoxic stress at baseline, implying a predictable transcriptomic signature for tamoxifen susceptivity. Moreover, immunoblotting showed that tamoxifen …
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Investigating coordination between stress-induced translational and transcriptional attenuation
… mitochondrial dysfunction, and oxidative stress are all common features of neurodegeneration. To date, there is little therapeutic intervention available to tackle neurodegenerative disease. Protein misfolding results in the activation of several stress-induced processes including the …
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