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 19 of 19 for “"Polyubiquitin chains"”.
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Structural characterization of interaction of K11 and K63 mixed-linkage polyubiquitin chains with the tUIMs of epsin1
… attachment of ubiquitin monomers within a polyubiquitin chain via a specific lysine residue. Thus the hypothesis is that linkage defines polyubiquitin conformation which in turn determines specific recognition by cellular receptors. Ubiquitylation of membrane surface receptor proteins plays …
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Liquid-Liquid Phase Separations in Innate Immune DNA Sensing and NF-κB Signaling Pathways
… NEMO activates IKK complex by binding to polyubiquitin chains. Here we show that Lys63(K63)-linked or linear(M1)-linked polyubiquitin chains binding to NEMO robustly induced the formation of liquidlike droplets in which IKK was activated both in vitro and in cells. Both NEMO ubiquitin …
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Biochemical Mechanism of Protein Kinase Activation by the Ubiquitination System
… TAK1-IKK cascade by TRAF6 and Ubc13/Uev1A in a polyubiquitinationdependent manner. Mechanistically how TAK1 is activated by the TRAF6- Ubc13/Uev1A dependent polyubiquitination system is unknown. Whether TAK1 and IKK kinases can be activated by other than TRAF6-Ubc13/Uev1A is an open question. By …
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Structural and biophysical analysis of the proteasomal deubiquitinase, UCH37
… for the disassembly of polymeric ubiquitin chains, or polyubiquitin, which have been ligated onto proteins in order to target them for degradation. The 26S utilizes two associated deubiquitinating enzymes, UCH37 and USP14, and one intrinsic, Rpn11, to remove polyubiquitin chains from …
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Decoding Lysine-11 Signals in Ubiquitination
… of ubiquitin in forming homo- or heterotypic chains on each of its seven lysine residues which in turn stimulate distinct downstream signaling pathways. These ubiquitin signals must be selectively initiated on the substrate protein and subsequently decoded to facilitate the desired cellular …
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Hrd1 Partners In Endoplasmic Reticulum-Associated Degradation
… suggesting that specific types of ubiquitin chains are formed in ERAD under varying conditions. These findings led us to wonder whether HRD1 makes different types of ubiquitin-ubiquitin linkages with different E2 ubiquitin-conjugases. Through in vitro reconstituted systems, we found that HRD1 …
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INSIGHTS INTO SUBSTRATE RECOGNITION BY THE ANAPHASE PROMOTING COMPLEX (APC)
… the anaphase promoting complex (APC). APC adds polyubiquitin chains to numerous substrates, which leads to their subsequent degradation in late mitosis and G1 phase. The selective and timely recognition and degradation of APC substrates is essential for proper cell cycle progression and …
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Quality control of protein complex assembly
… the KCMF1-UBR4 complex might build ubiquitin chains on pre-ubiquitinated orphans, thereby improving their recognition by the proteasome. *In vitro* reconstitution of orphan ubiquitination by the KCMF1-UBR4 complex showed that substrate pre-ubiquitination is both necessary and sufficient to …
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STRUCTURAL INSIGHTS INTO POLYUBIQUITIN CHAIN FORMATION MEDIATED BY NEDD4 HECT LIGASE
… with a single ubiquitin moiety or K63-linked polyubiquitin chains. Despite its critical role, the structural and mechanistic aspects of NEDD4-mediated polyubiquitination remain enigmatic. Our lab previously identified a ubiquitin exosite within HECT as critical determinant for enzyme …
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Biochemical and Genetic Studies on CC2D1A, a new NF-κB Activator and a Regulator of Synaptic Functions
… enzyme specific for Lysine-63 linked polyubiquitin chains, negatively regulates the activity of CC2D1A. These results suggest that CC2D1A activates NF-κB through the canonical IKK pathway. In an attempt to identify the physiological function of CC2D1A, I generated CC2D1A knockout mice. …
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SORTASE AND CHEMICAL BIOLOGY AS TOOLS TO STUDY UBIQUITINATION
… of proteins of interest with user-defined polyubiquitin chains. We exemplify the broad utility of this strategy for multiple different proteins of interest, including DNA replication protein PCNA. As an additional technology, we leverage this sortase-mediated ubiquitination system in …
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Ubiquitin Modulates Tollip's PtdIns(3)P Binding and Dissociates the Dimeric State of C-Terminal Cue Domain
… are conjugated either with monoubiquitin or polyubiquitin chains. Ubiquitin modifications on target proteins are recognized by ubiquitin-binding domains, which are found in several effector proteins. In this study, we describe for the first time how ubiquitin controls the function of the …
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Design and synthesis of molecular tools for the ubiquitin proteasome system
… of inhibiting Ubb+1 incorporation into long polyubiquitin chains. Remarkably, these antagonists proved to be selective towards Ubb+1 over ubiquitin despite the high degree of similarity in the relative binding sites of the two proteins. Further in silico design led to the development of a …
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Deubiquitinating Enzymes Promote Cancer Progression and Metastasis Via Regulating Protein Stability
… are enzymes that remove monoubiquitin or polyubiquitin chains from target proteins. DUBs have critical roles in cell homeostasis and signal transduction, as they regulate protein degradation, subcellular localization, and protein-protein interaction. Deregulation of DUBs contributes …
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Strengths and Weaknesses of Hybrid TPR Technology for Obtaining Structural and Mechanistic Insights into TPR Proteins
… regulators of the cell cycle are assembled with polyubiquitin chains by APC.</p> <p>One domain of the human APC is comprised of four related TPR proteins, APC8, APC6, APC3, and APC7, with each found in pairs. Crystal structures of some of these indicate that each has an N-terminal dimerization …
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Mechanisms of TRIM21-directed intracellular degradation
… binds and decorates the complex with these polyubiquitin chains. Polyubiquitin is a highly-conserved protein post- translational modification with a number of important roles, including the initiation of degradative processes and antiviral genetic programs. Polyubiquitin-coated …
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The Phase Behavior of Ubqln Proteins and Implications for Protein Quality Control
… UPS and autophagy signaled by ubiquitin (Ub) or polyubiquitin (polyUb) chains. Shuttle proteins facilitate cargo transporting by interacting with both ubiquitin and degradation machineries. Previously, our lab discovered that the shuttle protein Ubiquilin-2 (UBQLN2) is recruited to stress …
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Investigation into ubiquitin signalling in response to cisplatin
… is an E3 ubiquitin ligase that creates linear polyubiquitin chains as part of the linear ubiquitin assembly complex (LUBAC). LUBAC is required for innate and adaptive immunity, suppressing inflammation and the control of cell death through TNF and etoposide-induced signalling. HOIP was …
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Quantitative Deubiquitinase (DUB) Interactomics to Dissect the Biology of Cancer Associated DUBs
… deubiquitination is the removal of ubiquitin/polyubiquitin chains from ubiquitinated proteins. Deubiquitination is carried out by the class of enzymes called deubiquitinases (DUBs). These DUBs have vital roles in the regulation of protein ubiquitination and have a profound influence on the …