Global ETD Search
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Showing 1 to 13 of 13 for “"Aurora Kinase A"”.
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A study of novel tools to measure and perturb Aurora Kinase A protein stability
… novel ways to study the relative stability of Aurora Kinase A (AurKA). AurKA is a serine/threonine protein kinase that has well documented functions in the onset and progression of mitosis by promoting centrosome maturation and mitotic spindle assembly. The cognate pathway of AurKA degradation …
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SMARCA4/BRG1-Inactivating Mutations as Potential Predictive Markers for Aurora Kinase A-Targeted Therapy in NSCLCs
… RNA (siRNA)-based screening, we show here that Aurora kinase A (AURKA) activity is essential in NSCLCs carrying SMARCA4/BRG1-inactivating mutations. RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and diminish cellular viability in SMARCA4/BRG1-mutant NSCLC cells in …
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Targeting Transcription Factors in Neuroblastoma: Development of Aurora Kinase A/N-Myc Degraders and ID2 Chemical Probes
… degradation in neuroblastoma through binding to Aurora kinase A (Aurora-A). Chapters 2 – 3 will discuss the discovery of first-in-class Aurora-A/N-Myc degraders and the first proof-of-concept for targeting N-Myc with Aurora-A degraders. A highly selective and potent Aurora-A ligand 2.1 …
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Investigating The Interaction of Aurka and Ube2C In Colorectal Cancer Cells
… datasets showing its highest co-expression with Aurora kinase A (AURKA) pathway members, i.e. with AURKA and its binding co-factor and activator TPX2, all being localized on chromosome 20q. In addition, preliminary immunoblotting experiments in a panel of ten CRC cell lines showed high positive …
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Understanding the effect of allosteric regulation of Aurora kinases on inhibitor binding
Aurora kinase A and B regulate various signaling processes during mitosis, and their overexpression is associated with mitotic dysregulation and tumorigenesis. Many ATP-competitive inhibitors of Aurora kinases have been developed and are in various phases of clinical trials. However, the lack of …
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Preclinical Evaluation of Immunomodulatory Effects of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers
… a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human tumor cells in vitro and in vivo in HPV+ patient derived xenografts (PDX) mouse models. We hypothesized that Aurora kinase …
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Harnessing the Anaphase-Promoting Complex for Targeted Protein Degradation
… proteins including Securin, Cyclin B1 and Aurora kinase A. Most natural APC/C substrates contain multiple copies of short linear motifs (SLiMs), termed degrons, that serve as APC/C-recognition sequences. My research approach involved systematically dissecting various combinations of degrons …
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The Role of Stromal-Derived Factors in Neuroblastoma Differentiation
… DNA methyltransferases (DNMTs), and aurora kinase A (AurkA) can promote neuroblast differentiation and decrease proliferation. The combination of the DNMT inhibitor decitabine with the AurkA inhibitor MLN8237 enhances differentiation and reduces proliferation compared to either agent …
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Modulation of the aquaporin-2 localization in renal principal cells
… and the activation of the cAMP-dependent protein kinase (protein kinase A, PKA), the water channel aquaporin-2 (AQP2) is redistributed from intracellular vesicles into the plasma membrane of renal collecting duct principal cells. Its insertion into the plasma membrane induces the water …
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The Role of LIM Kinase 1 and its Substrates in Cell Cycle Progression
<p>LIM Kinase 1 (LIMK1), a modulator of actin and microtubule dynamics, has been shown to be involved in cell cycle progression. In this study we examine the role of LIMK1 in G1 phase and mitosis. We found ectopic expression of LIMK1 resulted in altered expression of p27Kip1, the G1 phase Cyclin …
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A novel route to oncogenic activation of cell cycle kinase Aurora A
Aurora kinase A (AURKA) is a major positive regulator of the cell cycle, required for the onset of mitosis and the completion of cell division. Recent research has uncovered roles of AURKA that are independent of the kinase activity and that regulate multiple cellular processes, including motility, …
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Cellular Determinants Of AURKA Degradation By Small Molecule Proteolysis-Targeting Chimeras
… influence PROTAC efficacy, using the oncogenic kinase Aurora kinase A (AURKA) as a model substrate. Many small molecule inhibitors of AURKA have failed during clinical development due to dose-limiting toxicities and the emergence of resistance mechanisms. MLN8237 (alisertib) is an example of a …
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Investigating how ubiquitin-mediated proteolysis of AURKA contributes to its activity in the cell cycle
Aurora kinase A (AURKA) is a major mitotic regulatory kinase required for mitotic entry, the formation of a bipolar mitotic spindle, and the completion of cytokinesis. In recent years AURKA has been identified as an upstream regulator for many interphase functions such as cilia disassembly and …