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 18 of 18 for “"Polo-like kinase 1"”.
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SYNTHETIC DOSAGE LETHAL INTERACTIONS OF POLO-LIKE KINASE 1 AND THEIR APPLICATION IN CANCER THERAPEUTICS
… in the identification of effective targets. Polo-like kinase 1 is overexpressed near ubiquitously across cancer types and dysregulation of polo-like kinase 1 is closely tied to chromosomal instability and tumour heterogeneity. Despite promising pre-clinical studies, clinical trials of …
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Determining Mechanisms of Response to Polo-Like Kinase 1 Inhibition In Non-Small Cell Lung Cancer
… data for a broad range of drugs. We identified polo-like kinase 1 (Plk1) as the most promising target for further investigation based on a subset of sensitive cell lines and inhibitors that were in advanced clinical development. To identify potential biomarkers of response and mechanisms of Plk1 …
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G2/M checkpoint associated repression of polo-like kinase-1 mediated by the tumour suppressor, p53
Polo-like Kinase-1 (PLK1) is an important mediator of the G2/M phase of the cell cycle that is down-regulated in a DNA damage dependent manner. In cancer cells PLK1 is overexpressed and allows for continued proliferation of the cell by overriding this checkpoint. Here I show that PLK1 is …
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Polo-Like Kinase 1 and Smooth Muscle Cells in Coronary Artery Bypass Conduits and Coronary Arteries Following Angioplasty
… unknown. In this study, we examined the role of polo-like kinase (PLK)-1 in the PLK1/pPLK1-pCDK1-p-Histone H3 pathway in mediating mitotic progression of smooth muscle cells (SMCs) from human IMA and SV in the development of IH leading to veingraft disease. We also show in vivo data in support of …
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EXPLORING THE CROSSTALK BETWEEN POLO-LIKE KINASE 1 AND Eph-FAMILY OF RECEPTORS IN CELL DIVISION IN PANCREATIC CANCER MODEL
… behaviour. This leads to upregulation of Polo-like kinase 1 (PLK1) a mitotic kinase and Receptor tyrosine kinases (RTKs) which promotes metastatic behaviour. Of the majority of Eph receptors EphA2 is overexpressed in many cancers and in PDAC as well. A wealth of literature has reported an …
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Epithelial to Mesenchymal Transition As A Predictor of Response to Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma
… with recurrent, advanced or metastatic NSCLC. Polo-like kinase 1 (PLK1), involved in the regulation of mitotic processes and the response to DNA damage, is overexpressed in NSCLC. Inhibiting PLK1 may be an effective treatment for NSCLC patients as it is involved in the mechanisms of resistance …
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Modulation of mitotic progression and cell cycle checkpoints by phosphorylation-dependent protein-protein interactions
… chromosomal aberrations and genomic instability. Polo-like-kinase-1 is a critical mitotic regulator, overexpressed in human tumors, that functions in mitotic entry after cellular stress, centrosome maturation, mitotic spindle control, and cytokinesis, which are all disregulated in cancer cells. To …
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The role of PLK1 in Hepatitis B Virus (HBV) infection of the liver
… infection and pathogenesis. I also identify Polo-like-kinase 1 (PLK1) as a proviral factor in HBV pathogenesis. I demonstrate by loss of function as well as gain of function approaches that PLK1 inhibition suppresses viral replication both in vitro and in vivo. I also show that HBc is a …
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Investigation of the role of p53 in protecting cancer cells against PLK1 inhibitors
The protein kinase Polo-like kinase-1 (PLK1) is an essential driver of mitosis and is oncogenic when expressed at elevated levels. Therefore, a number of inhibitors of PLK1 have been developed as potential anti-cancer therapeutic agents. While these inhibitors undergo clinical evaluation there has …
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Uncovering a fundamental mechanism underlying female oocyte quality and RASopathies using C. elegans as a model system
… growth factor signals through a downstream kinase cascade and ERK (Extracellular-signal regulated kinase) is the terminal kinase, and it controls cellular processes such as proliferation, differentiation, and survival by phosphorylating its downstream effectors. This post translational …
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Development of Non-Atp Competitive, Plk1-Selective Inhibitors
<p>Polo like kinase 1 (PLK1) is a member of a conserved family of serine/threonine kinases that plays an important role in the regulation of mitotic progression. PLK1 is over-expressed in a number of tumor types, thus making it a good therapeutic target. Because other PLK family members are …
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Mechanisms for the propagation and recognition of human centromeres
… propagation of the centromere. I identified Polo-like kinase 1 as a key player in controlling the deposition of the epigenetic mark that specifies the centromere, the CENP-A nucleosome. I defined the molecular basis for this control, as well as an additional level of control downstream of the …
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Probing the biology of liver fluke-flukicide interplay
… in vitro culture platform highlighted neoblast-like cells to be the drivers for fluke growth. Here, it was shown that these neoblast-like cells exhibit stem cell-like features, including the capacity for self-renewal and asymmetric division. Through irradiation and silencing of the cell-cycle …
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Structural and Molecular Mechanisms of Centrosome Assembly and Strength
The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry …
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Inhibition of PLK1 by p53 and by PLK1-targeted drugs
Polo like kinase 1 (PLK1) has many functions in the orchestration of cell division. It is an oncogene and its overexpression is associated with poor prognosis. PLK1 is a cell cycle-dependent protein; its levels are low in the early phases of the cell cycle and increase as cells go through the …
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Functional characterization of the novel centrosomal protein Nlp (ninein-like protein)
… component, the human protein Nlp (ninein-like protein) related to the previously characterized MT-anchoring protein ninein. In the first part of the present thesis we describe the identification of Nlp as a novel centrosomal substrate of Polo-like kinase 1 (Plk1), an important regulator of …
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Role of XRCC3 in Acquisition and Maintenance of Invasiveness through Extracellular Matrix in Breast Cancer Progression
… in the breast. It was previously shown that Polo-like kinase 1 (PLK-1), a mitotic kinase and genome stability regulator, is involved in acquisition of invasiveness in a breast cell model (HMT-3522 cell line) of pre-invasive to invasive transition. This and other data led to the suggestion …
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THERAPEUTIC POTENTIAL OF TARGETING THE FLNA-REGULATED WEE1 KINASE PATHWAY IN ADRENOCORTICAL CARCINOMAS.
… to its role in negatively regulating the insulin-like growth factor 1 receptor (IGF1R) signalling. Upregulation of Wee1 nuclear kinase, a key regulator of G2/M cell cycle checkpoint, was shown in mouse neural progenitor cells lacking FLNA, and it has been reported in several cancers. The first …