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Showing 1 to 20 of 172 for “"E3 ligase"”.
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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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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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Roles for the E3 Ligase Itch in Immune Response Modulation
… in the agouti mutant strain a has implicated the E3 ligase Itch in the spontaneous inflammation that occurs in these mice. 1 RH Anaylsis of a mice suggests that the inflammatory disease is due to a dysregulated T helper type-2 immune response. In order to verify the importance of Itch inactivation …
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Investigating the protein targets of the neuroprotective E3 ligase, CHIP
… proteostasis is the dual function chaperone and E3 ligase C-terminus of Hsc-70 interacting protein (CHIP). Its role in neurodegenerative diseases, including dementia with Lewy bodies, and the severe progeria and proteotoxic phenotype seen in CHIP KO mice support its neuroprotective effects, but …
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Regulation of the Parkin E3 ligase by PINK1-dependent phosphorylation
… Parkin encodes a RING-In Between RING-RING E3 ligase that normally resides in the cytoplasm and is<br/>regulated by autoinhibitory intramolecular interactions. PINK1 is a mitochondrial Ser/Thr kinase that is unique in possessing a N-terminal mitochondrial targeting sequence and three loop …
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Investigations into the Biological Roles of the E3 ligase Ariadne 2/TRIAD1
… of immune responses. Ariadne 2 is a RING finger E3 ligase and is part of the highly conserved RBR (RING-B-Box-RING) superfamily, however, little is known of its function in mammalian systems. To further examine the physiological role, Ariadne 2 deficient mice were generated. In a mixed …
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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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DISSECTING THE ROLE OF NEDD4 HECT E3 LIGASE AND ITS ISOFORMS IN CANCER
NEDD4 is a E3 ubiquitin ligase belonging to the HECT family and is composed by a N-terminal C2 domain, four WW domains and the catalytic C-terminal HECT domain. Different studies evidenced a correlation between NEDD4 overexpression and tumor progression and in some cases its proto-oncogenic …
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Ehrlichia chaffeensis E3 Ligase TRP120 Ubiquitinates Tumor Suppressor FBW7 for Degradation to Promote Infection
… E. chaffeensis TRP120 effector which has HECT E3 ubiquitin ligase activity, interacts with the host nuclear tumor suppressor F-BOX and WD domain repeating-containing 7 (FBW7). FBW7 is the substrate recognition subunit of the Skp1-cullin-1-FBOX E3 ubiquitin (Ub) ligase complex (SCF) known to …
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Exploring the link between RAG1 Cellular Distribution and Components of the CRL4DCAF1 E3 Ligase
… of RAG1 is dependenton DCAF1, the CRL4DCAF1 E3 ubiquitin ligase, and the 26S proteasome. RAG1 sequestration in nucleoli and nuclear puncta have been implicated in regulating its activity. RAG1 nucleolar egress and puncta formation are dependent on the same domain as DCAF1 association. We …
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The JBS-associated E3 Ligase UBR-1 Maintains Synaptic Glutamate Homeostasis and Regulates Neurotransmitter Balance
… JBS results from mutations in the gene UBR1, an E3 ubiquitin ligase that specifically targets proteins for proteasomal degradation. There are multiple UBR1 homologs in humans; however, mutations in UBR1 alone lead to JBS. Although it is known that loss-of-function mutations in UBR1 cause JBS, the …
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Artemis Interacts With The Cul4A Ubiquitin E3 Ligase Complex and Regulates The Cell Cycle Progression
… cycle regulation as a component of Cullin-based E3 ligase complex. I show that Artemis interacts with Cul4A-DDB1 ligase complex via a direct interaction with the substrate-specific receptor DDB2, and deletion mapping analysis shows that part of the Snm1 domain of Artemis is responsible for this …
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Functional characterization of poly(ADP-ribose) dependent ubiquitin E3 ligase in the DNA damage response
… Part A. Systematic screening of pADPr dependent E3 ligase functions in the DNA damage response 29 1. Identification of pADPr binding protein by using a 17K protein microarray 29 2. Bioinformatic analysis of pADPr binding proteins 35 3. pADPr dependent E3 ligase 38 4. pADPr dependent localization …
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Systematic C-degron activity profiling implicates conditional regulation of the CTLH E3 ligase complex in ribosome maturation.
Many E3 ubiquitin ligases recognise specific degron motifs located at protein termini, yet the physiological relevance of these N-degron and C-degron pathways remains poorly understood due to the limited number of validated substrates. Thus, the major aim of this thesis was to define how C-terminal …
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Mechanisms underlying substrate engagement by TRIM7 and TRIM21 and strategies for re-directing their E3 ligase activity
… TRIM7 and TRIM21. Both proteins are ubiquitin E3 ligases that ubiquitinate and degrade substrates. My work on TRIM7 has uncovered a unique molecular mechanism of substrate selection and explains why TRIM7 is reported to interact with unrelated and diverse substrates, ranging from cellular …
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Discovery and Effects of Pharmacological Inhibition of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors
… protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing …
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Mechanisms of translational control by the ubiquitin E3 ligase neural precursor cell expressed developmentally down-regulated gene 4-like, Nedd4-2
Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01
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Synthesis of Non-Steroidal Estrogen Receptor Proteolysis Targeting Chimeric Molecules (Protacs)
… the PROTAC design more useful, a small molecule E3 ligase peptide mimic is desirable. The HIF-1alpha E3 ligase destruction sequence utilized in the PROTAC design requires a hydroxylated proline residue for recognition by the VCB E3 ligase. The synthesis of a tetrahydrofuran-based hydroxyproline …
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Development of Protein Degraders Inspired by Chemical Modifications
… that Dha itself can function as the minimal E3 ligase-recruiting handle and that tighter ternary complex formation is favored. Mechanistic elucidation via inhibitor screening confirmed that the Dha-based degrader operates through the ubiquitin-proteasome system by recruiting a Cullin-RING E3 …
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