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 53 for “"constitutive activation"”.
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Regulation of flt3 gene expression in haematopoietic and leukaemic stem cells
… commitment of haematopoietic stem cells (HSCs). Constitutive activation of the Flt3/FL pathway is a key factor in enhanced survival and expansion in acute myeloid leukaemia (AML). Although there is extensive knowledge regarding mutations leading to the constitutive activation of Flt3 receptor …
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Absence of Enhancer of Zeste Homolog 2 Promotes the Progression of KRAS-Driven Pancreatic Ductal Adenocarcinoma
… cancer by 2030. Previous studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this …
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Molecular Characterization of Glioblastoma Cancer Stem Cells
… an adherent culture system and shown to have constitutive activation of the STAT3/NF-κB signaling pathways and upregulation of STAT3 and NF-κB-dependent genes. Gene expression profiling also found components of the Notch pathway as being deregulated in glioma CSC, which were sensitive to …
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Roles For Braf Kinase Activating Mutations In Melanoma: Microenvironmental Immunosuppression
… fraction of cutaneous melanomas, leading to constitutive activation of the MAP kinase pathway. This genetic lesion endows tumor cells with proliferative and survival advantages, and metastatic melanoma patients treated with the BRAF(V600E)-specific inhibitor, Vemurafenib, have shown dramatic …
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DISSECTING THE ROLE OF Β-CATENIN AND MYC IN GASTRIC TUMOR FORMATION
… remarkable processes that require the concerted activation and restriction of distinct gene-expression programs. The Wnt signaling pathway plays a prominent role in regulating the homeostasis of gastrointestinal epithelium by promoting stem cell maintenance, proliferation and cell fate …
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The role of mammalian target of rapamycin complex 1 in hepatic physiology and disease
… Confirming our studies with rapamycin, genetic activation or suppression of mTORC 1 increased and decreased liver size respectively, and rendered the liver insensitive to nutrients. Rendering the liver insensitive to nutrients also had functional consequences. In response to starvation, the …
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Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms
… mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through …
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The SYK tyrosine kinase suppresses autolysosome biogenesis via activation of mTORC1 in pancreatic cancer cell lines
… cancer, KRAS is frequently mutated, resulting in constitutive activation in 90% of pancreatic cancer cell lines. We previously showed that SYK is highly expressed in a subset of KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) cell lines. We demonstrated that SYK kinase inhibition with …
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Identification of transcriptional mechanisms downstream of nf1 gene defeciency in malignant peripheral nerve sheath tumors
… activating protein (GAP) whose mutation leads to constitutive activation of RAS and mitogen-activated protein kinase (MAPK) signaling in NF1 patientsf tumors. However, therapeutic targeting of RAS and MAPK have had limited success (Kalamarides, et al., 2012).</p> <p>In this study, we modulated …
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Redox Sensing By Yeast Hsp70 Facilitates Modulation of Protein Quality Control and The Cytoprotective Response
… to stably interact with Hsf1, resulting in constitutive activation of the heat shock response. Consistent with the in vitro findings, <em>ssa1-2CD </em>cells were compromised for <em>de novo </em>folding, post-stress protein refolding and in regulated degradation of a model terminally …
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Studies on signaling pathways induced by FLT3, an important oncogene in AML
… therapeutic target. FLT3 mutations cause constitutive activation of intrinsic tyrosine kinase of the receptor, leading to ligand-independent signal transduction. The aims of my studies have been to analyze the kinetics and specificity of FLT3 autophosphorylation in wild-type FLT3 and …
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Targeting the protein tyrosine phosphatase, SHP2, and PI3K in FLT3-ITD+ leukemia
… tyrosine kinase receptor (FLT3-ITDs) cause constitutive activation of the receptor and confer a poor prognosis in acute myeloid leukemia (AML). We hypothesized that Shp2 interacts with FLT3-ITD via protein complexes at tyrosine (Y) 768, 955, and/or 969 and that Shp2 and PI3K work …
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The role of p90 ribosomal S6 kinases (RSKs) in Steroid signalling
… the phospho-mimetic mutation used does not cause constitutive activation of the RSKs. Together considering all experiments it was illustrated that the RSKs have differential effects on SR signalling. All the RSKs increased AR and GR activity despite some contradictions within the data. RSK4 …
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REGULATION OF DEFENSE RESPONSES MEDIATED BY BON1 AND BAP2 IN ARABIDOPSIS THALIANA
… regulate the R gene suppressor of npr1-1, constitutive 1 (SNC1). In the Columbia (Col) accession of A. thaliana, the loss-of-function (LOF) bon1-1 mutant allele exhibits a growth defect phenotype (dwarfed plant). bon1-1 leads to constitutive activation of SNC1 which compromises normal plant …
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Characterisation of HIF2A targets identifies MYC as a key determinant of HIF2A dependency in ccRCC
… the vast majority of ccRCC cases and results in constitutive activation of HIF2A, making HIF2A an important clinical target. While HIF2A inhibitors are showing promising results in clinical trials, many patients do not respond and ultimately most patients progress. To improve our understanding of …
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Metabolic Regulation of Cellular Signaling
… increase in cytosolic acetyl-coenzyme A and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We recently identified coenzyme A (CoA), derived from the breakdown of acetyl-CoA, as the key metabolic signal that mediates a novel mechanism of calmodulindependent activation of …
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Molecular Mechanism of MDA5 RNA Sensing in Innate Immunity and Disease Pathogenesis
… dissociation from endogenous RNAs, resulting in constitutive activation of signalling pathways. In contrast, the partial loss-of-function I923V variant of MDA5 is type 1 diabetes (T1D) protective but increases vulnerability to viral infections. I showed how the I923V mutation causes hyperactive …
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Characterizing the role of p21-Activated Kinase 3 (PAK3) in AP-1-induced transformation
… is regulated through the transcriptional activation of the PAK3 promoter by AP-1 binding directly to a single site in the promoter. We also show that constitutive activation of PAK3 results in changes in cJun phosphorylation and an increase in AP-1 activity, which can be inhibited by a …
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Identifying and Inhibiting Cholesterol-Protein Interactions for Therapeutic Development
Constitutive activation of key proteins in cancer and autoimmune diseases is typically attributed to mutations in cell signaling axes or increased external stimuli. Accumulating evidence implicates perturbation of lipid levels caused by reprogrammed lipid metabolism in a variety of human diseases. …
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Probing Iron Accumulation in Sacchromyces cerevisiae Using Integrative Biophysical and Biochemical Techniques
… Aft1-1up strain in which iron regulon genes are constitutively activated and compared to that of Yah1p-depleted and wild type yeast. Constitutive activation of iron regulon genes does not alter the cellular iron distribution significantly. However disruption of Fe/S cluster assembly by Yah1p …
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