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 32 for “"KEAP1"”.
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TARGETING THE NRF2/KEAP1 INTERACTION
The Nrf2/Keap1 protein-protein interaction (PPI) regulates activity of the Nrf2 antioxidant and anti-inflammatory pathway. The transcription factor Nrf2 has been found to be a key mediator in the resolution of inflammation and the progression of chronic diseases. Most known inducers of the Nrf2 …
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Single cell analysis of Keap1-Nrf2 dynamics
… expression. Nrf2 is negatively controlled by Keap1, a sensor protein which allows Nrf2 to respond to changing cellular conditions. In the basal state, Nrf2 binds to two sites of a Keap1 dimer allowing its ubiquitination in a Cullin-3/Rbx1-dependent manner. In response to electrophiles and …
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Investigating the role of the Nrf2-Keap1 pathway in mitophagy
… Interestingly, another pathway, the Nrf2-Keap1 pathway, which acts as sensor for stress within the cell, is also activated and mediates several cytoprotective functions, including redox and intermediary metabolism homeostasis, and autophagy. Studies have also indicated crossover between …
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Identification of genotype-specific dependencies in Keap1-deficient lung adenocarcinoma
Lung adenocarcinoma (LUAD) remains the world's leading cause of cancer related mortality with an estimated two-hundred thousand new cases arising in 2019 in the United states alone. Molecular characterization of patient tumors has identified activating mutations in the small GTPase, KRAS, …
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Investigating Therapeutic Strategies to Target Metabolic Vulnerabilities of Nsclc Tumors With Mutant Keap1 Gene
… identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate …
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Dual regulation of transcription factor Nrf2 by Keap1 and the beta-TrCP/GSK-3 in cancer
… by Kelch-like ECH-associated protein 1 (Keap1) an E3 ubiquitin ligase substrate adaptor protein that recruits of cullin-3 (Cul3) to Nrf2 via its Neh2 domain. Nrf2 is also negatively regulated by phosphorylation by glycogen synthase kinase-3 (GSK-3) causing β-transducin repeat-containing …
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ANALYSIS OF ELECTROPHILE-INDUCED NRF2 GENE ACTIVATION
… are regulated by the thiol-rich sensor protein Keap1, which is an adaptor protein for Cul3-dependent ubiquitination and degradation of Nrf2. However, the links between site-specificity of Keap1 modification by electrophiles and mechanisms of Nrf2 activation are poorly understood. We studied the …
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Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression
… in NFE2L2, the gene that encodes NRF2; and KEAP1, the cytoplasmic regulator of NRF2. Since it became established that elevated NRF2 signalling provides a beneficial role to the tumour through enhancing proliferation, enabling survival in highly oxidative conditions and enhancing resistance …
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Regulation of transcription factors NRF2 and HSF1 in mediating cellular stress responses
The KEAP1/NRF2/ARE pathway is at the forefront of cellular defense. Induction of this pathway is protective against various conditions of stress such as oxidative stress and exposure to electrophiles. Conversely, failure to upregulate the pathway leads to increased disease susceptibility and …
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Targeting Nrf2 in Inflammation and Cancer
… sulfides reported to date. Nrf2 is regulated by Keap1, which targets it for degradation. Disruption of the Nrf2/Keap1 interaction results in Nrf2 activation. In this study, a novel cell-penetrating peptide, based on the Keap1-binding site of Nrf2, disrupted the Nrf2/Keap1 interaction, and …
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Inhibiting Protein-Protein Interactions using Rationally-designed Repeat Proteins
… between Kelch-like ECH-associated protein 1 (Keap1) and Nuclear factor erythroid-2-related factor (Nrf2) as well as the interaction between c-Myc and Myc-associated factor X (Max). In Chapter 3, computationally-designed peptides were grafted into the inter-repeat loops of CTPRs as well as into …
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Μελέτες σε μοντέλα Drosophila νευρο-εκφυλιστικών ασθενειών
… μοριακές συνοδούς, αλλά και το μονοπάτι Keap1/Nrf2 (Keap1/CncC στην Drosophila melanogaster). Με τη γήρανση, ωστόσο, η οποία προκαλεί επιδείνωση της λειτουργικότητας των συστημάτων του οργανισμού, προκύπτει διαταραχή και μείωση της ικανότητας του δικτύου αυτού. Έτσι, η πιθανότητα …
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Non-resolving pro-inflammatory macrophage polarization by super-low doses of bacterial endotoxin
… the response by focusing on the Nrf2 inhibitor Keap1. Here we show that chronic SLD-LPS results in an accumulation of Keap1 in mouse bone marrow-derived macrophages, an effect specific to chronic SLD-LPS, as high doses of LPS failed to induce Keap1. We suggest that this effect may be related to …
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Molecular mechanisms of cadmium toxic
… cadmium chloride (CdCl₂). The role of the Nrf2-Keap1-ARE pathway in the adaptive response of these cell lines to Cd exposure was examined, and the possible mechanism(s) involved in the protective response of garlic extracts to CdCl₂ were also investigated. Finally, this work examined changes in …
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Hormetic dietary phytochemicals from Western Canadian plants: Identification, characterization and mechanistic insights
… thiols and the recombinantly expressed protein Keap1, the principal negative regulator of Nrf2, supported a mechanism of QR activation involving covalent modification of Keap1 cysteines for the polyacetylenes and phthalides. Analysis of transcriptional changes in response to treatment with a …
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The role of DAXX in the selective autophagy receptor SQSTM1/p62 phase condensation
… has suggested the critical role of the p62-Keap1-Nrf2 pathway in combating the oxidative stress and maintaining the cellular redox homeostasis. To examine whether DAXX has an effect on redox homeostasis, Reactive Oxygen Species (ROS) assays and Dual-luciferase assays were applied, and …
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Constructing and deconstructing cancer using CRISPR-Cas9
… of this system for the discovery of novel Keap1 mutant-specific genetic dependencies, many of which could potentially be pursued for the clinical benefit of patients whose tumors harbor loss of function mutations in KEAP1 (~17% of lung adenocarcinoma patients). These results demonstrate the …
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Investigating the role of mitochondrial dysfunction in a Drosophila model of C9orf72 ALS/FTD
… factor erythroid 2–related factor 2 (NRF2)/Keap1 signalling pathway might play a role. I found that NRF2 was translocated to the nucleus suggesting an activation of the pathway. However, there were minimal changes to NRF2 targeting transcript genes although changes were observed using a …
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Mechanisms by which natural polyphenols regulate the expression of cytoprotective genes
… the Nrf2 protein is targeted by its inhibitor Keap1 for ubiquitination in the cytosol. Upon redox stress, induced by low molecular weight electrophiles, Nrf2 can evade ubiquitination and translocate into the nucleus, where it heterodimerizes with members of the small Maf family of transcription …
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Designed bifunctional proteins for induced degradation of androgen receptor in prostate cancer
… attached to a CTPR containing an E3 ligase KEAP1-binding peptide from the protein NRF2. Ternary complex formation between AR DBD, CTPR-NRF2-ARE and the E3 ligase KEAP1 was demonstrated using biophysical techniques, and the results of preliminary experiments assessing endogenous AR levels in …
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