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 60 for “"CDK2"”.
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Regulation of Ciz1 by Cyclin A-Cyclin Dependent Kinase 2 (CDK2) mediated phosphorylation
… the regulation of the protein Ciz1 by cyclin A-CDK2. Ciz1 promotes localisation of cyclin A-CDK2 to chromatin sites at the G1/S phase transition and this ternary complex promotes initiation of DNA replication. However, the mechanisms by which Ciz1 is regulated are not fully understood. Here, …
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Molecular and biochemical characterisation of phosphorylation-dependent NICD1 turnover: novel roles for CDK1 and CDK2
In the developing vertebrate embryo, segmentation initiates very early and in a species-specific manner through the formation of somites, which later give rise to the vertebral column, most skeletal musculature and dermis. Somites are gradually and periodically pinched off from the anterior end of …
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Loss of Chk1 Function and Exogenous Expression of Cyclin A1/Cdk2 Results in Apoptosis after the MBT in Early Xenopus laevis Embryos
… of two cell cycle components, Chk1 and cyclin A1/Cdk2, during apoptosis was studied during early development of Xenopus embryos. Chk1 is a serine/threonine kinase that inhibits the activity of cyclin-dependent kinases (Cdks) in response to unreplicated DNA. In the pre-MBT embryo, Chk1 is present, …
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Characterization of the molecular mechanisms underlying retinoic acid induced growth inhibition in MCF-7 human breast cancer cells.
… a down regulation of cyclin dependent kinase 2 (cdk2) and cyclin D1 gene expression and a profound down regulation of cdk2 activity. In contrast, no changes were seen in cdk4 expression or activity. We have further demonstrated that RA did not cause a change in the overall levels of expression of …
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Mechanisms of cell cycle remodeling at the MBT during the development of Xenopus laevis embryos
… partner of the cyclin dependent kinase, Cdk2. To study the program that drives cyclin E degradation and cell cycle remodeling at the MBT, embryos were treated with two cell cycle inhibitors, GST-D34Xic1 and XChk1. Injection of embryos with GST-D34Xic1, a stoichiometric inhibitor of cyclin …
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Protein kinases: Structure modeling, inhibition, and protein-protein interactions
… our research on cyclin dependent kinase 2 (CDK2) and glycogen synthase kinase-3β (GSK-3β). We prepared a non-redundant database from 303 available CDK2 PDB structures. We removed all structural anomalies and proceeded to use the CDK2 database in studying CDK2 structure in its different …
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Molecular cell cycle mechanisms of human prostate crcinoma insensitivity to TGF-β?
… the association of p21WAF1/Cip1/Sdi1 with the Cdk2/cyclin E complex in both normal and prostate tumor cells. However, there was no increase in the association of p15INK4B nor p27K1P1 with the Cdk/cyclin complexes. In normal cells, the increase in the association of p21WAF1/Cip1/Sdi1 with the …
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Anti-cancer Functions and Mechanisms of a pRb2/p130 Peptide Fragment
… to be able to inhibit the kinase activity of Cdk2. The region responsible for the inhibitory effect was further narrowed down to a 39-amino-acid sequence, which was named as Spa310. In this dissertation, the anti-cancer functions and mechanisms of Spa310 were studied. The synthesized Spa310 …
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Probing the Role of Nascent Helicity in Protein Function: p27kip1 as a Regulator of the Cell Cycle
… D1 and D2 (LH domain deletion mutant) with the Cdk2/cyclin A complex. Results from isothermal titration calorimetry (ITC) and kinase inhibition assays, show that the interaction and of either D1 or D2 with the Cdk2/cyclin A complex is less favorable relative to that of the p27-KID and that the …
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Targeting CDK to Prevent and Treat Retinoblastoma and other Cancers
… signature, which reports real-time activity of CDK2 (a potent target of most CDK inhibitors). Surprisingly, we found that CDK2 activity does not predict CDK2 inhibitor sensitivity. Instead, drug sensitivity is predicted by a subset of Protein Processing networks (e.g. translation, mRNA …
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Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis
… EZH2 and cyclin E, the enzymatic activator of CDK2, co-expresses with clinical significance in patient biopsies of triple-negative breast cancer (TNBC) compared to normal breast cancer. Thereafter we demonstrated CDK2 phosphorylates EZH2 endogenously on residue T416 in breast cancer cell lines …
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Physiological and pathological role of serine 96 phosphorylation in the regulation of androgen receptor
… of polyQ-AR by cyclin-dependent kinase 2 (CDK2) at serine 96 increases toxicity. This post-translational modification was enriched in neurons. Therefore, we hypothesized that phosphorylation of polyQ-AR at serine 96 modulates its function in response to activation of neuronal activity, a …
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Design of Non-ATP Competitive and Cell Cycle Specific CDK Inhibitors Targeting Cyclin Binding Groove
<p>CDK2/cyclin A and CDK4/cyclin D1 are validated targets for cancer drug discovery with ATP competitive compounds being the most common inhibitors. However, issues arising from the selectivity of current inhibitors have prevented clinical validation of these important targets. To generate cell …
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Funktion und Regulation von D- und E-Typ-Cyclin-Cdk-Komplexen während der Entwicklung von Drosophila
… der Entwicklung die Inaktivierung von Cyclin E-Cdk2-Komplexen. Es wird allgemein angenommen, dass Cyclin E-Cdk2-Komplexe durch Cyclin D-Cdk4-Komplexe reguliert werden. So phosphorylieren Cyclin D-abhängige Kina-sen das Retinoblastoma-Protein Rb, wodurch die Repression von Klasse I-Zielgenen des …
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Modulation von Zellzyklus- und Apoptoseregulation in humanen kolorektalen Karzinomzellen durch Butyrat und Acetylsalicylsäure
… Butyrat auf die Expression von p21Waf1/Cip1 und cdk2: Acetylsalicylsäure und Butyrat in höheren Konzentrationen reduzierten die Expression von cdk2 in HT-29 Zellen, in niedrigen Konzentrationen führte nur die Acetylsalicylsäure-Butyrat-Kombination zu einem Abfall des cdk2-Proteingehalts. Butyrat …
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Increasing IFN-[gamma] productivity in CHO cells through CDK inhibition
… have shown that the specific inhibition of the CDK2-CcnE complex through chemical inhibition leads to growth arrest and a subsequent increase in specific productivity. In addition, we have shown that the knockdown of CcnEl alone leads to increases in specific productivity. With the advent of …
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Molecular modeling and SAR studies of CDK5/p25 selective inhibitors
… was to design CDK5/p25 inhibitors selective over CDK2. Since we were targeting neurodegeneration we wanted to avoid any undesired cell cycle mediated apoptotic effects of CDK2 inhibition. The task was very challenging, because the two kinases possessed very high levels of sequence homology. In our …
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Cytoplasmic Cyclin E Mediates Resistance to Aromatase Inhibitors In Breast Cancer
… cycle inhibition of AIs through up-regulation of CDK2, Rb, and phospho-Rb in a reversible manner. Lastly, we show that LMW-E expressing breast cancer cells respond to dinaciclib but not palbociclib. Taken together, this study suggests that targeting CDK2 by inhibitors such as dinaciclib in …
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Regulatory Mechanisms of Mitotic Catastrophe Induced by Doxorubicin
… cycle profiles using FACS, activities of Cdc2 or Cdk2. RESULTS: LD doxorubicin induced abnormal mitosis and then senescence-like phenotype (SLP) in Huh-7 human hepatoma cell lines. Subsequently, these cells were undergoing cell death through mitotic catastrophe which was caused by abnormal …
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Lmw-E Mediates Mammary Tumorigenesis By Deregulating Acinar Morphogenesis & Generating Cancer Stem Cells
… E is the regulatory subunit of the cyclin E/CDK2 complex that</p> <p>mediates the G1-S phase transition. N-terminal cleavage of cyclin E by elastase in</p> <p>breast cancer generates two low molecular weight (LMW) isoforms that exhibit both</p> <p>enhanced kinase activity and resistance to …
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