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Showing 1 to 20 of 53 for “"E3 ligases"”.
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Interaction Between Two E3 ligases, NEDD8ylated Cullin and HHARI
… between RING-RING2) is a special type of E3 ubiquitin ligase containing three zinc-binding RING (Really Interesting New Gene) domains, while adopting mechanisms of HECT (Homologous to E6-AP Carboxyl Terminus) for substrate ubiquitination. Most well known RBRs include Parkin and HOIP, which …
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The Role of Two Homologous E3 Ligases In Muscle Physiology
… enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligases. There are an estimated 600 E3 ligases, some of which share high sequence homology; however, the functional significance often remains unknown. FBXL3 and FBXL21 are two homologous E3 ligases that have previously been reported to …
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MECHANISMS OF SUBSTRATE DEGRADATION AND RECRUITMENT BY CULLIN E3 LIGASES
… protein degradation, is mediated by the Cullin E3 ubiquitin ligase family. The aim of this study is to achieve a better understanding of the function and regulation of Cullin E3 ligases. We studied the degradation of insulin receptor substrate 1 (IRS1) by the Cullin5 E3 ligase, and found that …
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Origins and composition of the cullin-RING E3 ligases in trypanosomes
… the E2s and eventually their recruitment to an E3 ligase that will transfer it to the substrate. Cullin-RING is a prominent family of E3 ligases responsible for ubiquitylation of up to 20% of the human proteome. In contrast with the rest of the class, cullin-RINGs perform their function as …
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Identification and Regulatory Role of E3 Ligases in the Time-Dependent Degradation of the Circadian Factor Period 2
… times, we found that inhibition of Mdm2 E3 ligase activity promoted phase advance only when treatment took place during the degradation period. This is in agreement with our findings that radiation, but not light pulses, causes the same phase behavior. Considering the established role of …
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Role of the RING domain in MDM2-mediated ubiquitination of 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 RING domain are traditionally thought to catalyse the transfer of ubiquitin from their conjugating enzyme (E2) partner to the …
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New Mass Spectrometry Approaches to Investigate Proteins and Protein Interactions
… interactions that essential proteins called E3 ligases have in cells. Eukaryotic cells use hundreds of unique E3 ligases to control cellular functions through protein degradation. E3 ligases selectively bind to protein substrates through recognition motifs known as degrons. The integrative MS …
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Fragment-based approaches to probe the surface of the VHL E3 ligase
… involved in the control of protein homeostasis, E3 ubiquitin ligases are emerging as interesting targets for the development of chemical probes and drugs. Small-molecule modulation of E3 ligases can provide several advantages over other members of the ubiquitin-proteasome system (UPS), as E3 …
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Functional Interactions of E2~Ubiquitin Conjugates in and outside the Ubiquitination Pathway
… transfer pathway are well established (E1, E2, E3), the molecular details required for protein ubiquitination are largely unknown. To address questions regarding the final stages of Ub transfer, we began with structural characterization of the pathway intermediate, the E2~Ub conjugate (~ …
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ELUCIDATION OF REGULATORY MECHANISMS OF TRANSCRIPTION AND COUPLED mRNA EXPORT
… in mRNA export via HECT domain-containing E3 ligases like Tom1 and Rsp5. My work has revealed the role of an F-box protein (Mdm30) component of RING domain-containing SCF (Skp-Cullin-F-box) family of E3 ligases in mRNA export, thereby implicating the role of ubiquitylation in export via …
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Ubiquitin E3 ligase mediated regulation of HMG-CoA Reductase
… of HMGCR with Insig proteins, which recruit E3 ubiquitin ligase complexes to mediate degradation of HMGCR by the ubiquitin proteasome system. However, the identity of the E3 ligase(s) responsible for HMGCR ubiquitination is controversial. Here, I use a series of genome-wide CRISPR knockout …
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Designed bifunctional proteins for induced degradation of androgen receptor in prostate cancer
… artificial modular scaffolds, onto which AR- and E3 ligase-binding moieties were grafted to induce AR ubiquitination and degradation. As the degraders bind AR through protein-protein interactions, we can effectively target sites distant from the ligand-binding pocket that are not affected by …
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Advancing understanding of endogenous PINK1-Parkin signalling linked to Parkinson’s disease
… (Ub) at Ser65, thereby activating Parkin E3 Ub ligase activity. Upon activation, Parkin ubiquitylates multiple proteins at the mitochondrial surface, triggering degradation of mitochondria or mitochondrial membrane proteins.<br/><br/>Our understanding of the PINK1-Parkin pathway is mainly …
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Protein-Protein Interactions and Small Molecule Targeting of the Multisubunit SOCS2-EloBC-Cul5-Rbx2 E3 Ubiquitin Ligase
The Cullin-RING E3 ligases (CRLs) are the largest subfamily of E3 ligases that participate in many biological processes determining the fate of proteins by catalysing ubiquitin transfer to specific substrates for proteasomal degradation. SOCS2 is a component of the multisubunit CRL E3 complex …
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BTB-Kelch Proteins and TAk1 Kinase N Immune Function
BTB-kelch proteins are putative components of E3 ligases with a BTB domain at the N terminus and several kelch repeats at the C terminus. KLHL6 and mKELCH are two members of this family. Conditional ablation of Klhl6 in B cells resulted in mild developmental phenotypes in bone marrow precursors. …
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STRATEGIES TO TARGET HUMAN D-ASPARTATE OXIDASE AND MODULATE ENDOGENOUS D-ASPARTATE LEVELS IN SCHIZOPHRENIA
… to recruit Cereblon or Von Hippel–Lindau (VHL) E3 ligases, respectively. These compounds were tested both in vitro and in cell lines for the interaction with DASPO and E3 ligases, and for the formation of ternary complexes necessary for DASPO proteasomal degradation. Among them, PROTAC 1 showed …
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The ubiquitin coat of cytosol-invading bacteria
… pathogen and evades targeting by host E3 ligases. In this work, I developed SPLINT Labelling, a novel tool to artificially induce ubiquitylation of S. flexneri by enforcing the recruitment of a Salmonella-targeting E3 ligase to the surface of Shigella. I demonstrate that SPLINT …
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Regulation of Anaphase Promoting Complex/Cyclosome to Control M Phase Exit
… Promoting Complex/Cyclosome (APC/C) is a RING E3 ligase that plays essential roles both within and outside of the cell cycle. At the onset of anaphase, the APC/C targets cyclin B and securin for degradation, initiating chromosome separation and mitotic exit. Regulation of APC/C activity is …
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Design and Synthesis of an E3 ligase Activity-Based Probe and its Application for the Discovery of a New Class of E3 Ligase
… The distinct transfer cascade, involving E1-E2-E3 enzymes, serves as a promising target for drug development. However, E3 ligases (E3s) represent an important class of enzymes yet there are currently no effective tools for profiling their activity. Herein, a new class of E3 activity-based probe …
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Identification of novel components of the zinc homeostasis mechanism in Arabidopsis thaliana
… to form a complex with cullin 4 ubiquitin E3 ligases and take part in the selective degradation of substrate proteins via the ubiquitin proteasome pathway. Single putative orthologs of this gene are found in Homo sapiens, D. melanogaster, C. elegans, X. laevis etc. However, functional …
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