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 31 for “"Polo-Like Kinase"”.
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The role of Polo-like kinase 2 in synaptic function and plasticity
… activity, the activity-inducible protein kinase, Polo-like kinase 2 (Plk2), was required for synaptic scaling in dissociated culture and for reducing membrane excitability in slice culture-two principal compensatory mechanisms underlying homeostatic plasticity. Inhibition of Plk2 activity …
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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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Small Molecules as Probes for Cell Division and Intracellular Transport
… by 4 inhibitors including one that targets Polo-like kinases, evolutionarily conserved serine/threonine kinases. Using chemical inhibitors and high-resolution live-cell microscopy, I found that Polo-like kinase activity is needed for the assembly and maintenance of bipolar mitotic spindles. …
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Control of M-G1 phase-specific expression in fission yeast
… mid1+/dmf1+ and plo1+, the latter encoding a Polo-like kinase that also regulates M-G1 gene expression and influences the PCB-dependent binding properties of PBF. Three transcription factors, Sep1p and Fkh2p, both forkhead-like transcription factors, and Mbx1p, a MADS-box protein, have been …
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Regulation of meiosis I chromosome segregation by Spol3 and Cdc5 in Saccharomyces cerevisiae
… meiosis I regulators, a mitotic protein kinase, Cdc5 and a meiosis-specific gene, Spol 3. The conserved polo-like kinase Cdc5 regulates many essential aspects of meiosis I including the removal of cohesion between sister chromatids for homolog segregation, sister-kinetochore …
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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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The PLK1 and NLRP3 interactome in NLRP3 inflammasome activation
… Our unpublished work has identified the Polo-like kinase (PLK1) as a potential regulator of the NLRP3 inflammasome pathway. Using two different methods, I showed that PLK1 interacted with NLRP3 and that that interaction was enhanced during NLRP3 inflammasome activation. Moreover, I …
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REGULATION OF CHROMOSOME SEGREGATION BY CONSERVED PHOSPHATASE CDC14 AND KINASE CDC5
… pathways, the FEAR network and the MEN. As the polo-like kinase Cdc5 is a component of both pathways its activity is essential to Cdc14 release and in its absence Cdc14 is never released. By combining loss-of-function alleles of Cdc5 and Cdc14 we obtained double mutant cells that had cohesin …
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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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Consequences of Plk4 overexpression in mouse pancreatic organoids
Overexpression of the polo-like kinase 4 (Plk4), the master regulator of centrosome duplication, leads to centrosome amplification, a common feature of cancer, including pancreatic cancer. Previous studies have shown that overexpression of Plk4 in mice carrying a doxycycline-inducible Plk4 …
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Roles for motifs of cell cycle regulating kinases beyond substrate selection of individual kinases
… and cancer formation. Several protein kinases, including the major mitotic kinases Cdkl, Aurora A, Aurora B, Nek2, and Plkl, and the Polo-like kinase (Plk) family, Plkl, Plk2, Plk3, and Plk4, are known to play important roles in the regulation of mitosis and other phases of the cell …
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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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