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Showing 1 to 20 of 23 for “"20S proteasome"”.
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Metabolism of Alpha-Synuclein by the 20S Proteasome
… forms cause dysfunction of the ubiquitin-proteasome pathway of protein degradation, thereby enhancing an alternative pathway that involves ubiquitin-independent degradation by the 20S core particle of the proteasome. The 20S proteasome is known to degrade proteins with regions of intrinsic …
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Substrate Selection by the 20S Proteasome and Implications in Disease Pathogenesis
… forms of alpha-synuclein produced by the 20S proteasome in vitro, through a ubiquitin-independent mechanism, are similar to those found in the cingulate cortex of patients with Lewy body diseases. The work presented here describes an investigation into the mechanism by which …
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Compromising the 20S Proteasome Activates a Quality Control Pathway to Mitigate Proteotoxic Stress
<p>The regulation of the ubiquitin-proteasome system (UPS) has been the subject of a vast body of work because of its implication in normal development and a wide range of diseases. The UPS controls the degradation of a large number of cellular proteins and thereby regulates essential cellular …
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Metal complexes of non-heme ligands: biological applications
… (carbonic anhydrase–I, trypsin, chymotrypsin and 20S proteasome) by non–heme iron complexes, and glutathionylation of non–heme cobalt complexes mimicking the N5 coordination environment like that of biologically important cofactor cobalamin or B<sub>12</sub> (Cbl) are reported. Different non–heme …
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Design and synthesis and testing of conformationally constrained peptidomimetics.
… inhibition of calpain, α-chymotrypsin and the 20S proteasome. Chapter Four reports the in vitro testing of macrocycles 3.02, 3.03 and 3.04 against calpain II and discusses these results in the context of the SAR study completed by the Abell group to identify the criteria for the most potent …
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Synthesis of proteasome inhibitors: analogues of nelfinavir
… effect on chymotrypsin-like activity of 20S proteasome. Previous studies also show the promotion of acceleration of the apoptosis process within cancer cells by inhibition of proteasome activity. Separate experiments proved nelfinavir 1 to be involved in the inhibition of Akt pathway – an …
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Cooperativity and communication in archaeal Cdc48·20S, an ancient proteolytic machine
… enzyme and binding to its partner peptidase, the 20S proteasome. In this thesis I present experiments which investigate the role of inter-ring communication in ATP hydrolysis, protein unfolding, and allosteric interactions with the 20S and show how these features affect enzyme function. …
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The effects of Parkinson's disease mimetics on the proteasomal and neurofilament systems in SH-SY5Y cells
… factors influence the various activities of the proteasome in SH-SY5Y human neuroblastoma cells treated with the PD mimetics MPP+ (a complex I inhibitor) or dopamine. Treatment with these toxins led to dose and time dependent reductions in ATP and glutathione levels and also chymotrypsin-like and …
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Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis
… other ubiquitinated proteins without inhibiting 20S proteasome activity. Further analysis of the mechanism of action of WP1130 revealed that WP1130 acts as a partly selective DUB inhibitor. It specifically inhibits the deubiquitinase activity of USP9x, USP5, USP14 and UCH37. WP1130 mediated …
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Investigation of the potential bacterial proteasome homologue Anbu
… significant homology to the sub-units of the 20S proteasome and is predicted to be a novel bacterial proteasome. The goal of this project was to determine if the recombinant Anbu protein from Pseudomonas aeruginosa is a proteasome. Anbu from P. aeruginosa was successfully cloned, expressed and …
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Effects of mitochondrial dysfunction on neurofilament turnover and distribution in human neuroblastoma cells
… cathepsin, but not calpain or the ubiquitin proteasome system (UPS). This is in contrast to α-synuclein which was degraded by macroautophagy, the UPS and calpain. Treatment with MPP+ did not increase NF halflife despite a reduction in the activity of the 20S proteasome, cathepsin D and …
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Strategies for the synthesis of bioactive compounds: biomimetic approaches to the Salinosporamides and the hexadehydro-Diels-Alder reaction
… moiety. These molecules are known to inhibit the 20S proteasome (20SP) by utilizing the β-lactone reactivity, a promising target for cancer therapeutics. We propose that salinosporamide A may be formed biosynthetically by a non-enzymatic bis-cyclization event involving an uncatalyzed …
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Customising lactacystins: studies towards the total synthesis of lactacystin and its analogues
… to inhibit the chymotrypsin-like activity in the 20S proteasome.
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Interrogating novel functions of the I kappa B kinases via CRISPR-Cas9 gene editing and small molecule inhibition
… of NEMO to in vitro degradation by the 20S proteasome was examined, with NEMO proving be a highly effective substrate of the 20S proteasome. Importantly, IKKα and IKKβ were both shown to protect NEMO from proteasomal degradation, leading us to propose a model whereby interaction with IKK …
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A study of the expression and cellular function of the human FAM111B gene
… interaction with G3V3W4, a component of the 20S proteasome complex involved in the proteolytic degradation of damaged proteins, may suggest the rapid clearance of this mutant protein.
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A Role for PI31-Mediated Proteasome Regulation in Proteostasis and Neuronal Health
… of proteins is achieved by the Ubiquitin-Proteasome System (UPS), which governs a variety of cellular processes such as apoptosis, cell cycle progression, protein quality control, and metabolism. Using this system, cells maintain homeostasis by quickly and irreversibly altering signaling …
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PORPHYRIN DERIVATIVES AS VERSATILE PROTEASOME MODULATORS
The ubiquitin proteasome system (UPS) is the primary degradation system in eukaryotic cells, with high selectivity for a myriad of soluble proteins, and perturbations in the UPS are associated with numerous human disorders. For this reason the proteasome has become a pharmacological target for …
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The proteasome and its ancillary proteins
The proteasome is an essential multi-protein complex found within all eukaryotes. It degrades unwanted proteins and is involved in regulating many cellular functions, including cell homeostasis and apoptosis. Previous research in the field mainly focused on the mechanisms by which substrate …
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Advancing T Cell–Based Immunotherapies: Identification of Tumor-Specific T Cell Receptor Targets and Mechanisms of Resistance in Solid Tumors
… cell lung cancer model. This screen revealed proteasome subunit alpha 7 (PSMA7), a core component of the 20S proteasome, as a critical immune regulator. PSMA7 is overexpressed across multiple cancer types, and its upregulation leads to poor prognosis. We discovered that loss of PSMA7 in tumor …
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Development of Surface Plasmon Resonance and Top-Down Mass Spectrometry Approaches to Monitor the Conformational Properties of Amyloidogenic Peptides and Their Enzymatic Cleavage: a Specific Application to Uncover the Mechanisms of Digestion of Branched Ubiquitin-Tau Proteoforms by the Human 20S Proteasome [Sviluppo di approcci di risonanza plasmonica di superficie e spettrometria di massa top-down per monitorare le proprietà conformazionali dei peptidi amiloidogenici e la loro digestione enzimatica: un'applicazione specifica per scoprire i meccanismi di digestione delle proteoforme ramificate di ubiquitina-tau da parte del proteasoma umano 20S]
… 4RD-tau sono state somministrate al Proteasoma 20S umano (h20S). Sono stati quindi applicati esperimenti di SDS-PAGE e spettrometria di massa top-down (MS) per studiare il modello di degradazione delle proteoforme tau e per monitorare il rilascio dei frammenti di digestione. Lo sviluppo di un …
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