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 15 of 15 for “"MLKL"”.
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Thioredoxin-1 Inhibition Promotes MLKL Activation: Biochemical Insights Into a Suppressor of the Necroptotic Pathway
… been discovered including RIP1/3 kinases and MLKL, which together, form the core of the necrosome complex. RIP3-dependent phosphorylation of MLKL promotes the formation of high molecular weight MLKL polymers that disrupt the integrity of the plasma membrane leading to cell death. However, the …
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Optimization of Receptor-Interacting Protein Kinase 2 (RIPK2) Inhibitors and Development of Mixed Lineage Kinase Domain-Like (MLKL) Activators
… activator of mixed lineage kinase domain-like (MLKL) pseudokinase as the final effector of the necroptosis cell death pathway. Previously, our lab discovered compound UH15-22 capable of binding MLKL and inducing necroptosis. However, the compound displayed off-target activity and low binding …
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The Role of CK1 in Necroptosis and Confirmation of Amyloid-Like Fibers in Necroptosis Using 2D SDD-AGE
… and mixed-lineage kinase domain-like protein (MLKL). Phosphorylation of human RIPK3 at serine 227 (S227) has been shown to be required for downstream MLKL binding and necroptosis progression. Tandem immunoprecipitation of RIPK3 reveals that casein kinase 1 (CK1) family proteins associate with …
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Exploring The Relationship Between Mitochondrial-linked Cell Death And Muscle Atrophy During Ovarian Cancer Progression
… while necroptosis markers (RIPK1, phosphorylated MLKL/total MLKL) decreased with cancer progression. EOC-induced changes in necroptosis were unaffected by SkQ1, whereas markers of apoptosis (caspase-3/-9 activities) were downregulated by SkQ1. This study lays a crucial foundation for future …
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Functional and Mechanistic Analysis of Protein Degradation by Human Cytomegalovirus to Uncover Viral Immune Evasion Mechanisms
… mixed lineage kinase domain-like pseudokinase (MLKL) and DmX-like protein 1 (DMXL1), were then selected for further mechanistic and functional characterisation. MLKL is the terminal effector of a form of cell death called necroptosis. Many herpesviruses suppress necroptotic signalling to evade …
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Characterisation of Novel Autophagy and Necroptosis Antagonists Encoded by Human Cytomegalovirus
… which targets mixed lineage kinase-like protein (MLKL) for degradation, and IE1, which enhances the ubiquitination of receptor-interacting protein kinase 3 (RIPK3). A systematic screen of HCMV recombinants lacking blocks of accessory genes dispensable for viral replication indicated that deleting …
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Mode of Entry and Survival of Salmonella Enterica Serovar Typhimurium in Trophoblast Cells
… phosphorylated-mixed lineage kinase domain-like (MLKL), suggesting induction of the necroptosis pathway of cell death. Furthermore, specific inhibition of necroptosis rescued S.Tm-induced death of cTBCs. Finally, S.Tm infected trophoblast cells produced interleukin (IL)-10, and signal transducer …
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Non-resolving pro-inflammatory macrophage polarization by super-low doses of bacterial endotoxin
… by accumulation of autophagy flux markers MLKL and p62. Further, we show that these effects are dependent on the non-traditional TLR4 adaptor TRAM, suggesting an alternative dose-dependent signaling pathway for LPS. Together this work identifies novel signaling mechanisms involved in …
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Study of Regulated Cell Death In Two Systems: Pd-1 In Natural Killer Cells and Rip3 In Neurons
… mixed lineage kinase domain-like pseudokinase (MLKL) and mitochondrial apoptosis-inducing factor (AIF). Inhibiting RIP3 by an FDA approved anti-cancer drug, dabrafenib, reduced both acid-induced death of mouse cortical neurons <em>in vitro</em> and brain infarction in mice subjected to middle …
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Exploiting tumour cell dependency on pro-survival BCL2 proteins with BH3 mimetics
… through the binding of the effector protein MLKL, which was displaced upon BCL-XL inhibition. BH3 mimetics are effective as single agents for the treatment of haematological malignancies, but their application in solid tumours needs to be refined. The results presented here demonstrate that …
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The anti-cancer activity of extracts derived from millets and Kraalbos
… 3, 7, 8, and 9 and PARP) and necroptosis (p-MLKL and p-RIP3) KB2 was found to induce cell death via the intrinsic and extrinsic apoptotic pathways and necroptosis. Western blotting and immunocytochemistry with an antibody to LC-3 also showed that KB2 induces autophagy in the breast cancer …
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Identifying novel drugs for the treatment of rhabdomyosarcoma
… levels of necroptotic markers p-RIP3 and p-MLKL and inhibition of necroptosis with necrostatin-1 with a corresponding significant increase in cell viability suggests that AJ-5 is also capable of triggering a form of programmed necrosis. Furthermore, AJ-5 reduced autophagic flux as shown by …
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Discovery of Novel Mechanisms Regulating Cancer Extravasation in the Chorioallantoic Membrane Model
Cancer metastasis is a multistep process that begins with the invasion of tumour cells into the stroma and migration towards the blood vessels. Tumour cells that have entered the bloodstream must then survive and leave by a process known as extravasation. Finally, extravasated cells proliferate and …
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Role of RIP3 in DNA damaging agent-induced breast cancer cell death
Receptor-interacting protein kinase 3 (RIP3 or RIPK3) is a central player in “programmed” or “regulated” necrotic cell death pathway. Here we show that programmed necrosis is activated in response to chemotherapeutic agents and contributes to chemotherapy-induced breast cancer cell death. However, …
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Loss of Caspase-8 Function In Combination With Smac Mimetic Treatment Sensitizes Head and Neck Squamous Carcinoma to Radiation Through Induction of Necroptosis.
<p>Caspase-8 (CASP8) is one of the most frequently mutated genes in Head and Neck Squamous Carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has …