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 “"TBK1"”.
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Molecular Mechanisms Underlying Innate Immune Kinase TBK1-Driven Oncogenic Transformation
An essential kinase in innate immune signaling, TBK1 couples pathogen surveillance to induction of host defense mechanisms. The pathological activation of TBK1 in cancer can overcome programmed cell death cues, enabling cells to survive oncogenic stress. The mechanistic basis of TBK1 prosurvival …
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Identifying Protein Kinase Tbk1 As A Novel Inhibitor of Intestinal Tumorigenesis
… serine/threonine kinase, TANK Binding Kinase 1 (TBK1). Although TBK1 is best known as a mediator of type I interferon induction in antiviral innate immunity, recent evidence suggests the involvement of TBK1 in several other biological processes including cancer development. Based on <em>in …
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The Non-canonical Function and Regulation of TBK1 in the Cell Cycle
… leading to cancer. Tank Binding Kinase 1 (TBK1) is overexpressed in certain cancer types and is activated on the centrosomes during mitosis. Loss of TBK1 impairs cell division resulting in growth defects and the accumulation of multinucleated cells. Therefore, proper activation and …
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Loss of TBK1 Kinase Function Improves Disease Outcome in Pancreatic Cancer and Metabolic Syndrome
… and activity of TANK binding kinase 1 (TBK1) has been observed in numerous diseases. Here I've identified novel functions for TBK1 in pancreatic ductal adenocarcinoma (PDA) and in metabolic syndrome that promote disease progression. Activating mutations in KRAS are present in 90% of …
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THE ROLE OF INTERFERON REGULATORY FACTORS IN REGULATING THE EXPRESSION OF NKG2D LIGANDS
… damage depends on the serine/threonine kinase TBK1 and its phosphorylation target IRF3. The activation of IRF3 in response to DNA damage was evidenced by its phosphorylation and nuclear translocation. TBK1 is upstream of IRF3 and similarly, its phosphorylation was observed during DNA damage. …
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A Host Regulatory Circuit of HSV Gene Expression
… K11- and K48-linked ubiquitination. Furthermore, TBK1 mirrors the results of STING, independently of IFN, upon viral infection. As such, ablation of STING or TBK1 rescues viral production. Mechanistically, STING acts with TBK1 and the E3 ligase TRIM23. This model supports the idea that STING …
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THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY
… activation of a kinase, TANK binding kinase 1 (TBK1), which phosphorylates the downstream transcription factors, IRF3 and IRF7, and leads to the production of IFN-beta. Interestingly, TBK1 function has been implicated in a number of other signaling cascades ranging from the insulin response and …
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Developing Novel Therapies Targeting the Tumor Microenvironment of Aggressive Breast Cancer
… synergy targets. We found TANK-binding kinase 1 (TBK1) to be the top therapeutic candidate due to its critical role in immune responses. Strikingly, combined suppression of AXL and TBK1 significantly reduces IBC and TNBC growth in vitro and in vivo by modulating the immunosuppressive TME. …
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An Investigation into the Effects of Macrophage Polarisation on Interleukin-1 Expression
… of amplified IL-1 in M2s guided us to explore TBK1 signalling, which revealed that TBK1 inhibition significantly decreased IL-1α in M2s, but increased IL-1β in M0 and M1 macrophages. We also observed that this subtype-specific effect on IL-1 was not dependent on type I interferon or IRF3 …
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The Sec6/8 (a.k.a. Exocyst) Complex Supports DNA Repair Fidelity
… pathway through the innate immune protein TBK1 (TANK-binding kinase 1). siRNA-mediated depletion of TBK1 in pancreatic and breast cancer cell lines results in apoptosis, which is mediated through the AKT pathway. Pharmacological inhibition of TBK1 recapitulates the apoptotic phenotype in …
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Charakterisierung der viralen Genprodukte p10 und P des Borna Disease Virus
… IRF3 durch die zelluläre Kinase TBK1 und somit dessen Aktivierung. Der Befund, dass P mit TBK1 Komplexe bildet und zudem auch als Substrat für die zelluläre Kinase fungiert, erlaubt es, erstmalig einen Mechanismus zu postulieren, in dem ein virales Protein (BDV-P) als putatives …
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Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma
… sensitivity to clinical MEK inhibitors versus TBK1/IKBKE inhibitors. Importantly, subtype membership can be predicted using a robust quantitative 5-feature genetic biomarker. This biomarker, or the mechanistic relationships linked to it, can identify a cohort of best responders to clinical MEK …
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The role of the DEAD box Helicase DDX3X in Anti-‐Viral Signalling Pathways Mediated by the Kinase IKKα.
… signalling in pathways mediated by IKKε and TBK1. In this work we show that DDX3X is also involved in pathways independent of these kinases, and functions by interacting with two related kinases IKKα and NIK. DDX3X enhances the activation of IKKα and subsequently, augments the activation of …
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LUBAC is required for the RIG-I mediated antiviral response
… activation of IRF3 and NF-κB in this context. TBK1 and IKKε were shown to function redundantly to activate IRF3 but not NF-kB. Linear ubiquitin chains are produced exclusively by the tripartite E3 ligase LUBAC, made up of HOIP, HOIL and SHARPIN, and are required for NF-κB activation by PRR such …
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Novel protocols to induce tolerance to solid organ transplants
… undergo metabolic re-programming and switch to TBK1/IKKe/AKT-induced glycolysis at the early activation phase, which is sustained due to nitric oxide (NO)-mediated inhibition of mitochondrial metabolism at the later activation phase. Targeting DC activation in the view of promoting less …
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Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3
… adaptor recruiting and activating TBK1, the kinase for IRF3 phosphorylation. Those results offered insights into the mechanism underlying IRF3 activation mediated by K63-linked polyubiquitination.
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Characterization of The Roles of Carma3 and Bcl10 In Virus-Triggered Rig-I/Mavs Signaling Pathway
… which forms a prion-like structure to recruit TBK1and IKK complex to activate IRF3 and NF-κB, respectively. Herein, we revealed the important roles of CARMA3 and BCL10 in RIG-I/MAVS signaling pathway for the first time. CARMA3 or BCL10 deficient cells exhibited partially defective NF-κB …
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Identification and Characterization of Auxiliary Factors in Innate Antiviral Immunity
… SRMS loss led to diminished phosphorylations of TBK1 and IRF3, IRF3 dimerization, and nuclear translocation. The kinase activity of SRMS, however, was dispensable. Reconstituting the expression of SRMS of mouse or human origin, be it wild-type or kinase-dead protein, in SRMS-null MEFs restored …
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Functional Analysis of the Molluscum Contagiosum Virus MC160 Death Effector Domain-Containing Protein RxDL Motif
… motifs were assessed for the ability to inhibit TBK1- and MAVS- induced activation of interferon-β. Surprisingly, the RxDL mutants retained the ability to inhibit IFN-β activation as assessed by the activity of a firefly luciferase gene under the control of the IFN-β enhancer. Therefore, the RxDL …
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