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 24 for “"Aurora Kinase"”.
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THE ROLE OF AURORA KINASE IN THE DEVELOPING MALE GAMETOPHYTE OF MARSILEA VESTITA
… mitotic division. I investigated the roles of aurora kinases in the formation and maturation of the blepharoplast. Three unique aurora kinase isoforms were found in the transcriptome of the male gametophyte, each with a unique N-terminal sequence and expression pattern. RNAi knockdowns of each …
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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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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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The regulation of chromosome segregation by Aurora kinase, protein phosphatase 1 and nucleolar protein UTp7
… opposes in vivo functions of the Ipl1-Sli15-Bir1 kinase complex in budding yeast. I show here Scd5- a targeting subunit of Glc7 that regulates endocytosis/cortical actin organization and undergoes nuclear-cytoplasmic shuttling- is present at kinetochores. Ipl1 associates with both Glc7 and Scd5. …
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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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Novel combination strategies with Aurora Kinase Inhibitors: using pre-clinical data to guide clinical trial design
… strategies combining current drugs with aurora kinase inhibitors (AKI) in pre-clinical models and then to design a clinical trial to assess these in patients with bladder cancer. Particular interest was stimulated by the correlation between over-expression of aurora kinases (AKs) with …
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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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The Influence of Cellular Redox State on Mitosis
… dynamic network of well-characterized protein kinases, ensuring cells only transition to subsequent cell cycle stages when specific checkpoints have been passed. This regulation prevents cells with insufficient biomass, incomplete DNA replication, or misaligned chromosomes from dividing into …
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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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Exploring the effects and efficacy of novel cell cycle regulating compounds in aggressive Breast, Ovarian and Cervical Cancer
… The commercial compounds Reversine (an Aurora kinase B and Mps1 inhibitor) and Apcin (an APC/C inhibitor) have been established to be cytotoxic to cancer. This thesis aimed to confirm the efficacy of these compounds and to test the cytotoxicity of three novel small molecules that …
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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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Regulation of Set1-Mediated Methylation of Dam1
… phosphorylation of adjacent serines by the Ipl1 Aurora kinase. The discovery of a second Set1 substrate raised the question of how Set1 function is regulated at the kinetochore. I hypothesized that transcriptional regulatory factors essential for H3K4 methylation at gene promoters might also …
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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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Investigating the C-terminal region of RalA: regulation through membrane dynamics and protein-protein interactions
… effects of phosphorylation of RalA at Ser194 by Aurora kinase on membrane interactions. Phosphorylation of this residue appears to have consequences for membrane interaction that extend beyond the HVR to the G-domain of the protein, demonstrating that this short intrinsically disordered region of …
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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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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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Studies of Aurora and Polo Kinases During Cell Division in C. elegans
… Using C. elegans, we investigated the roles of Aurora and Polo kinases during the release of meiotic chromosome cohesion. We found that the Aurora B kinase AIR-2 is localized to sub-chromosomal regions representing the last points of contact between homologous chromosomes in meiosis I and …
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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 …
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