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 86 for “"MDM2"”.
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Role of MDM2 In Cell Growth Regulation
MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK …
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Targeting the p53/MDM2 protein-protein interaction
The p53/MDM2 protein-protein interaction is the most widely characterised proteinprotein interaction to date. As of 2014, there are over 20 compounds that have been shown to the p53-MDM2 protein-protein interaction, however many compounds have not progressed into clinical trials due to their high …
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Preclinical Pharmacology of the MDM2 Antagonist Nutlin-3a
<p>Nutlin-3a is an MDM2-p53 interaction antagonist that is under investigation in preclinical models for a variety of pediatric malignancies, including neuroblastoma, retinoblastoma, leukemia, and rhabdomyosarcoma. In the current research, we conducted preclinical pharmacology studies of nutlin-3a …
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Therapeutic Efficacy of P53 Restoration In Mdm2-Overexpressing Tumors
… Other mechanisms, <em>e.g.</em> upregulation of Mdm2 levels, exist in tumors to inactivate the p53 pathway. Mdm2, an E3 ubiquitin-ligase that targets p53 for proteasomal degradation, is present at high levels in many tumors with wild-type p53. In this study, we probed the effects of restoring p53 …
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Engineering a synthetic p53-Mdm2 network in budding yeast
… p53 ubiquitylation by the E3 ubiquitin ligase Mdm2 - an event central to the oscillatory dynamics of the system - does not appear to take place in budding yeast, even when the human E2 enzyme UbcH5B is exogenously expressed. p53 is instead sumoylated by Mdm2 and sumoylation dictates the …
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The Consequences of Disrupting The Mdm2-P53 Balance In Hematopoiesis
… a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis progresses normally during embryogenesis until it moves to the bone marrow in late development. Increased oxidative …
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Contrasting Effects of An Mdm2 Functional Polymorphism On Tumor Phenotypes
… polymorphisms with cancer risk. The <em>MDM2 SNP309G</em> allele is a cancer-associated functional polymorphism positioned in the <em>MDM2</em> P2 promoter that enhances transcription factor SP1 binding, resulting in elevated levels of MDM2 concomitant with decreased p53 tumor-suppressor …
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Targeting The Mdm2-P53 Axis For The Treatment of Dedifferentiated Liposarcoma
… discovery of improved therapeutic approaches. MDM2 is a well characterized oncoprotein and the most known negative regulator of p53. <em>MDM2</em> amplification is considered the “hallmark” of DDLPS. Additionally, these tumors are known to harbor wild-type p53. We sought to take advantage of …
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Veränderungen am Protoonkogen MDM2 bei Urothelkarzinomen in Bezug auf bekannte Risikofaktoren
… charakterisiert. Auf Gen-Ebene gilt MDM2 als zentrales Onkogen und Antagonist von p53, dessen Spleissvarianten (SV) wesentliche Effekte auf die Tumorgenese zugeschrieben werden. Ziel der Studie war die Frage nach der Korrelation von klinischen Daten (Expositionsanamnese, …
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Role of the RING domain in MDM2-mediated ubiquitination of p53
The MDM2 protein regulates the tumour suppressor protein p53, acting as its chaperone, regulating its translation and targeting p53 for degradation by the 26s proteasome via its E3 ligase activity. The E3 ligase activity of MDM2 is dependent on its C-terminal RING domain. E3 ligases containing a …
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Re-thinking the role of ribosomal proteins in the Mdm2-p53 axis
The Mdm2-p53 axis is an important pathway in cells that is frequently misregulated in cancer. Under basal conditions, Mdm2 suppresses p53 through multiple mechanisms. However, when stress is encountered, this suppression is lifted and p53 transactivates the expression of many target genes to effect …
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Investigating MDM2 Regulation of Endothelial Cell Angiomir Biosynthesis in Response to High Glucose Treatment
… exposure to high glucose concentrations enhances MDM2:DROSHA binding and represses DROSHA expression both in vitro and in diabetic mice (db/db) muscles. Treatment with MDM2 inhibitors repealed glucose-induced DROSHA downregulation. This suggests that high glucose concentrations downregulates …
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INTERPLAY BETWEEN MDM2 AND TFAM REGULATES OXIDATIVE PHOSPHORYLATION IN DRUG-RESISTANT ONCOGENE-ADDICTED CANCERS
… a novel mechanism involving mitochondria-bound MDM2 (mtMDM2) in driving OXPHOS regulation in TKI-resistant cancers through an interaction with TFAM. This phenomenon involves the mitochondrial-cytoplasm shuttling of MDM2 in a p53-independent manner, which leads to enhanced mitochondrial …
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The study of Murine double minute-2 (Mdm2) in regulating neuronal activity-dependent protein translation
… a novel function of Murine double minute 2 (Mdm2), an ubiquitin E3 ligase, which is involved in the Gp1 mGluR-mediated translational control and activation leads to the elevation of neural activity. Using a fragile X syndrome (FXS) mouse model, we demonstrated this phenomenon is modulated by …
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ScRING finger protein, Mdm2, MdmX, p53, cancer, ubiquitination, drug discovery, ZINC16046951, University of Zululand, South Africa
… protein. In silico inhibitory studies, for Mdm2 and MdmX complexes with RO-2443 as a control, and ZINC16046951, as the experimental ligand, were conducted using molecular dynamics tools, namely RMSD, RMSF and Rog. MM/PBSA and MM/GBSA were utilized to calculate binding free energy …
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Mdm2-Mediated Degradation of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis and Trastuzumab Resistance In Breast Cancer
… SIRT6 at Ser<sup>338</sup> and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser<sup>338</sup> phosphorylation prevents its degradation by MDM2 and results in inhibition of cell proliferation and breast …
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Using Stable Limit Cycles to Model p53-Mdm2 Protein Interactions in the Presence of DNA Damage
… and destroyed within a cell. Another protein, Mdm2, is a negative regulator of p53. In the presence of DNA damage, Mdm2 does not bind to p53, thus activating the p53 protein. This activation then promotes the mechanisms necessary to either fix or terminate the damaged cell. The concentration of …
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Context Dependent Roles of MDMX (MDM4) and MDM2 in Breast Cancer Proliferation and Circulating Tumor Cells
… cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. Expression of MDM2 and MDMX occurs in both estrogen receptor α positive (ER+) and triple negative breast cancer (TNBC). We and others have reported that estrogen activated MDM2 strongly promotes proliferation in ER+ T47D …
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Phospho-regulation and metastatic potential of Murine Double Minute 2
Murine double minute (Mdm2) is a highly modified and multi-faceted protein that is overexpressed in numerous human malignancies. It engages in many cellular activities and is essential for development since deletion of mdm2 is lethal in early stages of embryonic development. The most studied …
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Epitranscriptional Control of the Caspase-2—MDM2—p53 Axis: The Role of the m6A Writer in p53 Signaling.
… suppressor pathway, acting through the Caspase-2–MDM2–p53 signaling axis, provides a crucial surveillance mechanism that detects centrosome aberrations and prevents the propagation of genomically unstable cells. Despite significant progress in understanding the proteolytic events driving this …
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