TY - JOUR. T1 - Modulating cellular balance of Rps3 mono-ubiquitination by both Hel2 E3 ligase and Ubp3 deubiquitinase regulates protein quality control. AU - Jung, Youjin. AU - Kim, Hag Dong. AU - Yang, Hee Woong. AU - Kim, Hye Jin. AU - Jang, Chang Young. AU - Kim, Joon. PY - 2017/11/3. Y1 - 2017/11/3. N2 - When a ribosome complex is stalled during the translation elongation process in eukaryotes, the mono-ubiquitination of Rps3 has recently been shown to be critical to ribosome quality control. We have discovered that the regulatory role of Rps3 mono-ubiquitination is controlled by a deubiquitinase. We also showed that an autophagic signal appears to be coupled to the mono-ubiquitination of Rps3p through the entrance of Ubp3p into the autophagosome in yeasts. The mono-ubiquitination of the Rps3 protein is tightly modulated by reciprocal action between the Hel2p E3 ligase and the Ubp3p deubiquitinase in yeasts and the reciprocal action between the RNF123 E3 ligase and the USP10 deubiquitinase ...
Linear ubiquitination is definitely a important posttranslational adjustment that regulates immune system signaling and cell death pathways, notably tumor necrosis element receptor 1 (TNFR1) signaling. caspase\8 or epidermal mutilation of FADD.21, 23 These studies collectively corroborate a central part of LUBAC in restraining aberrant service of TNFR1\induced cell death machineries in order to maintain cells homeostasis. Although mice show liver swelling, it remains unfamiliar which cells and cell types contribute to hepatitis. In addition, the physiological part of LUBAC in LPCs remains unfamiliar. Here, we looked into the part of linear ubiquitination and Rabbit Polyclonal to MMP-19 LUBAC in liver swelling and carcinogenesis by studying mice that lack HOIP, the central and catalytically active component of LUBAC, specifically in LPCs. Materials and Methods ANIMALS All animal studies were carried out relating to an appropriate license under the Animals (Scientific TSA Methods) Take action of ...
E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates Lys-48-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Also ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate apoptosis downstream of death domain receptors. Also negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling.
Author Summary Polycomb-group (PcG) proteins play essential roles in the epigenetic regulation of gene expression during development. PcG proteins form two distinct multimeric complexes, PRC1 and PRC2. In the widely accepted hierarchical model, PRC2 is recruited to specific genomic locations and catalyzes trimethylation of H3 lysine 27 (H3K27me3), thereby creating binding sites for PRC1, which then catalyzes mono-ubiquitination of histone H2A (H2AK119u1). Recently, PRC1 has been shown to be able to compact chromatin structure at target loci independently of its histone ubiquitination activity. Therefore, the role of H2AK119u1 still remains unclear. To gain insight into this issue, we used ChIP-on-chip analysis to map H2AK119u1 genome-wide in mouse ES cells (ESCs). The data demonstrate that H2AK119u1 occupies a distinctive subset of genes with H3K27me3 enrichment. These genes are the central targets of Polycomb silencing to maintain ESC identity. We further show that the H2A ubiquitination activity of
Regulates signaling cascades probably through protein ubiquitination and/or sequestration. Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation. Inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA. May be a substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity ...
The attachment of one or more ubiquitin moieties to proteins plays a central regulatory mechanism in eukaryotic cells. Protein ubiquitylation regulates numerous cellular processes, including protein degradation, signal transduction, DNA repair and cell division. The characterization of ubiquitylation is a two-fold challenge that involves the mapping of ubiquitylation sites and the determination of ubiquitin chain topology. This review focuses on the technical advances in the mass spectrometry-based characterization of ubiquitylation sites, which have recently involved the large-scale identification of ubiquitylation sites by peptide-level enrichment strategies. The discovery that ubiquitylation is a widespread modification similar to phosphorylation and acetylation suggests cross-talk may also occur at the post translational modification level ...
The ubiquitin E1, E2, and E3 ligase enzymes are the enzymatic core of the ubiquitination pathway. The E2-E3 complex interacts with the substrate, catalyzing ubiquitin addition to the substrate. Thus, the expression, activity, localization, and selectivity of ubiquitin E2s and E3s are important parameters that can serve to regulate ubiquitination. The E2-E3 combination used in the ubiquitination reaction can also influence the fate of the substrate through determining the extent and nature of ubiquitin addition. The majority of substrates observed to date are modified by the attachment of a Lys-48-linked ubiquitin chain, which targets the substrate for degradation by the 26S proteasome. Substrates modified with other types of polyubiquitin chains linked via ubiquitin Lys-6, -11, -29, and -63, or modified with a single ubiquitin, face different or unknown fates. For example, the heterodimeric E2 UBC13/methyl methane sulfonate sensitivity 2 functions with the RING E3 TNF receptor-associated factor ...
In this study, we examined the potential mechanism responsible for COMMD1‐mediated repression of NF‐κB and its ability to accelerate the dissociation of RelA from chromatin (Burstein et al, 2005). Interestingly, others had reported that ubiquitination of RelA also accelerates its release from chromatin (Saccani et al, 2004), suggesting that ubiquitination of RelA might be responsible for the effects of COMMD1. Indeed, we present evidence that COMMD1 promotes the ubiquitination of NF‐κB subunits and our data also indicate that this effect is mediated by the interaction of COMMD1 with ECSSOCS1, a Cullin‐containing ubiquitin ligase complex previously implicated in RelA ubiquitination (Ryo et al, 2003). These events are physiologically important because COMMD1 deficiency results in de‐repression of several endogenous NF‐κB‐responsive genes and enhanced κB‐mediated cellular responses such as the production of chemokines. Finally, our studies indicated that the role of COMMD1 in ...
Vascular calcification (VC) often associates with many cardiovascular and metabolic diseases. Although VC is the cause of high morbidity and mortality, molecular mechanisms have yet to be elucidated. Here we report that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity enhanced VC in vivo and in vitro. HDAC1 protein was reduced in cell and animal calcification models and in human calcified coronary artery and this reduction preceded VC. Calcification stresses induced MDM2 E3 ligase, which resulted in HDAC1 K74 ubiquitination. Forced expression of MDM2 enhanced VC, whereas loss of MDM2 blunted it. A decoy peptide spanning HDAC1 K74 prevented VC. These results demonstrate a previously unknown ubiquitination pathway as well as the involvement of HDAC1 in VC. Our results suggest MDM2-mediated HDAC1 ubiquitination as a new therapeutic target in VC. ...
Whenever a ribosome complex is stalled through the translation elongation procedure in eukaryotes, the mono-ubiquitination of Rps3 has been shown to become critical to ribosome quality control. critically modulate Hel2p/RNF123-mediated Rps3p mono-ubiquitination. Furthermore, we discovered that Hel2p/RNF123 and Ubp3p/USP10 were in a different way localized in the ribosome complicated after ultraviolet irradiation. Jointly, our outcomes support a model where coordinated ubiquitination and deubiquitination actions can finely stability the amount of regulatory Rps3p mono-ubiquitination in ribosome-associated quality control and autophagy procedures. Launch The ribosome is certainly macromolecular machinery thats responsible for proteins synthesis.1 However, several ribosomal protein have already been found to possess extra-ribosomal features, including tension response,2, 3 the induction of apoptosis4 and repairing both mitochondrial and nuclear DNA harm.5, 6 For instance, its been reported that ...
The transcription factor zinc-finger protein Miz1 represses TNF-α-induced JNK activation and the repression is relieved upon TNF-α stimulation. However, the underlying mechanism is incompletely understood. Here we report that Miz1 interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the RING domain of TNF-receptor associated factor 2 (TRAF2), thereby inhibiting the ubiquitin ligase (E3) activity of TRAF2 and suppressing TNF-α-induced JNK activation. Upon TNF-α stimulation, Miz1 rapidly undergoes K48-linked polyubiquitination at Lys388 and Lys472 residues and subsequent proteasomal degradation in a TRAF2-dependent manner. Replacement of Lysine 388 and Lysine 472 by arginines generates a nondegradable Miz1 mutant, which significantly suppresses TNF-α-induced JNK1 activation and inflammation. Thus, our results reveal a molecular mechanism by which the repression of TNF-α-induced JNK activation by Miz1 is de-repressed by its own site-specific ubiquitination and ...
Because NF-κB pathways make key contributions to host defense mechanisms, the activation of NF-κB is tightly controlled by endogenous regulators acting at several sites. Ubiquitination regulates at least four steps in NF-κB pathways, including targeting IκBα for degradation, processing of NF-κB precursors to produce p50/p52 subunits of NF-κB, and activation of kinases such as receptor-interacting protein or the regulatory subunit of the IKK complex IKKγ (NEMO) and activation of TRAF-family adapter proteins (TRAF2, TRAF6) (9, 35, 36). Ubiquitin is a 76-aa protein that is covalently attached to target proteins through an isopeptide bond, between the C terminus of ubiquitin and the ε-amino group of a lysine residue in the target proteins (9, 37). Ubiquitin contains seven lysine residues, but ubiquitin chains linked on Lys48 and Lys63 are the best characterized, to date. Whereas Lys48-linked polyubiquitin chains represent a signal for proteosomal degradation of modified substrates such as ...
Author summary Viruses have much smaller genomes than their hosts. Consequently, they often encode proteins which are multifunctional. For instance, some viral proteases have a dual function, being also deubiquitinases, i.e. enzymes capable of removing ubiquitin tags grafted onto proteins and that often target them for destruction. The protease and deubiquitinase activities share a single active site that is used alternately for one function or the other, but how this switch between activities may be regulated is presently unknown. To answer this question, we studied a simple plant virus that is a useful model system for these complex molecular biology phenomena, and that encodes a simplified protease/deubiquitinase. Here, thanks to a combination of structural and functional analyses, we managed to decouple the two activities, killing the deubiquitinase activity while preserving the protease one. This successful decoupling relies on our discovery that a loop inserted next to the active site is mobile,
Selective degradation of proteins in the cell occurs through ubiquitination, which consists of post-translational deposition of ubiquitin on proteins to target them for degradation by proteases. However, ubiquitination does not only impact on protein stability, but promotes changes in their functions. Whereas the deposition of ubiquitin has been amply studied and discussed, the antagonistic activity, deubiquitination, is just emerging and the full model and players involved in this mechanism are far from being completely understood. Nevertheless, it is the dynamic balance between ubiquitination and deubiquitination that is essential for the development and homeostasis of organisms. In this review, we present a detailed analysis of the members of the deubiquitinase (DUB) superfamily in plants and its division in different clades. We describe current knowledge in the molecular and functional characterisation of DUB proteins, focusing primarily on Arabidopsis thaliana. In addition, the striking function of
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology ...
Mcl-1 is an anti-apoptotic protein of the Bcl-2 family that is essential for the survival of multiple cell lineages and that is highly amplified in human cancer. Under physiological conditions, Mcl-1 expression is tightly regulated at multiple levels, involving transcriptional, post-transcriptional and post-translational processes. Ubiquitination of Mcl-1, that targets it for proteasomal degradation, allows for rapid elimination of the protein and triggering of cell death, in response to various cellular events. In the last decade, a number of studies have elucidated different pathways controlling Mcl-1 ubiquitination and degradation. Four different E3 ubiquitin-ligases (e.g., Mule, SCFβ-TrCP, SCFFbw7 and Trim17) and one deubiquitinase (e.g., USP9X), that respectively mediate and oppose Mcl-1 ubiquitination, have been formerly identified. The interaction between Mule and Mcl-1 can be modulated by other Bcl-2 family proteins, while recognition of Mcl-1 by the other E3 ubiquitin-ligases and
The Signal Seeker Ubiquitination enrichment Kit can purify ubiquitnated or Ubiquitylated, antibody, mono-ubiquitin, polyubiquitin, ubiquitin chains, sumoylation, proteosome, mono-ubiquitination, signal transduction, signal pathway and affinity beads.
Background: Ubiquitination is a vital posttranslational protein modification involved in the regulation of many eukaryotic signalling pathways. Aberrant ubiquitin signalling is known to be a molecular causality of certain cancer, neurodegenerative, immune system or cardiovascular diseases. The recent development of mass spectrometry methods enables qualitative and quantitative ubiquitination...
The data reported herein provide evidence that hKOR undergoes agonist-dependent ubiquitination, and its ubiquitination regulates, but is not required for, sorting of internalized receptor to degradation pathway. Agonist-promoted ubiquitination of the hKOR, which occurs at Lys residues in the C-terminal domain of the hKOR, is enhanced by hKOR phosphorylation but unchanged by receptor internalization. In addition, agonist-promoted polyubiquitination of the hKOR occurs predominantly as Lys63-linked polyubiquitin chains. To the best of our knowledge, this is the first report that Lys63-linked polyubiquitination of a 7TMR is involved in its down-regulation.. Ubiquitination of the hKOR Regulates, but Is Not Required for, Agonist-Induced hKOR Down-Regulation. Ubiquitination of the hKOR was increased substantially after agonist stimulation. The rapid occurrence of ubiquitination of the hKOR after agonist incubation (30 min) is similar to that reported for several 7TMRs, including the β2-AR (within 15 ...
TY - JOUR. T1 - Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. AU - Hao, Yi Heng. AU - Doyle, Jennifer M.. AU - Ramanathan, Saumya. AU - Gomez, Timothy S.. AU - Jia, Da. AU - Xu, Ming. AU - Chen, Zhijian J.. AU - Billadeau, Daniel D.. AU - Rosen, Michael K.. AU - Potts, Patrick Ryan. PY - 2013/2/28. Y1 - 2013/2/28. N2 - Endosomal protein trafficking is an essential cellular process that is deregulated in several diseases and targeted by pathogens. Here, we describe a role for ubiquitination in this process. We find that the E3 RING ubiquitin ligase, MAGE-L2-TRIM27, localizes to endosomes through interactions with the retromer complex. Knockdown of MAGE-L2-TRIM27 or the Ube2O E2 ubiquitin-conjugating enzyme significantly impaired retromer-mediated transport. We further demonstrate that MAGE-L2-TRIM27 ubiquitin ligase activity is required for nucleation of endosomal F-actin by the WASH regulatory complex, a known regulator of retromer-mediated ...
Rationale: Hypoxia followed by reoxygenation promotes inflammation by activating NF-κB transcription factors in endothelial cells (EC). This process involves modification of the signalling intermediary TRAF6 with polyubiquitin chains. Thus cellular mechanisms that suppress TRAF6 ubiquitination are potential therapeutic targets to reduce inflammation in hypoxic tissues. Objective: In this study, we tested the hypothesis that endothelial activation in response to hypoxia-reoxygenation can be influenced by Cezanne, a deubiquitinating enzyme that cleaves ubiquitin from specific modified proteins. Methods and Results: Studies of cultured endothelial cells (EC) demonstrated that hypoxia (1% oxygen) induced Cezanne via p38 MAP kinase-dependent transcriptional and post-transcriptional mechanisms. Hypoxia-reoxygenation had minimal effects on pro-inflammatory signalling in unmanipulated EC but significantly enhanced Lys-63 polyubiquitination of TRAF6, activation of NF-κB and expression of inflammatory ...
SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor.
Protein ubiquitination is a key regulatory process essential to life at a cellular level; significant efforts have been made to identify ubiquitinated proteins through proteomics studies but the level of success has not reached that of heavily studied post-translational modifications such as phosphorylation. of more than 400 ubiquitinated Phentolamine HCl proteins a fraction of which were found to be sensitive to HRD1 and were therefore deemed candidate substrates. In a second approach ubiquitinated peptides were enriched after tryptic digestion by peptide immunoprecipitation using an antibody specific for the diglycine-labeled internal lysine residue indicative of protein ubiquitination with peptides and ubiquitination sites identified by LC-MS/MS. Peptide immunoprecipitation resulted in identification of over 1800 ubiquitinated peptides on over 900 proteins in each study with several proteins emerging as sensitive to HRD1 levels. Notably significant overlap exists between the HRD1 substrates ...
Malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. For example, BAP1 encodes a widely expressed deubiquitinase for histone H2A, but germline mutations are predominantly associated with uveal melanomas and mesotheliomas. We show that BAP1 inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver, and pancreatic tissue but not in melanocytes and mesothelial cells. Ubiquitin ligase RNF2, which silences genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing expression of the prosurvival genes Bcl2 and Mcl1. In contrast, BAP1 loss in melanocytes had little impact on expression of prosurvival genes, instead inducing Mitf. Thus, BAP1 appears to modulate gene expression by countering H2A ubiquitination, but its loss only promotes tumorigenesis in cells that do not engage an RNF2-dependent apoptotic program.
Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. May act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival ...
Background May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target...
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a constitutively-expressed HIF-1beta subunit. Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxia, HIF-1 alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors ...
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a constitutively-expressed HIF-1beta subunit. Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxia, HIF-1 alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors ...
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a constitutively-expressed HIF-1beta subunit. Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxia, HIF-1 alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors ...
Ubiquitination, also known as ubiquitylation, is an enzymatic process that involves the bonding of an ubiquitin protein to a substrate protein. This has sometimes been referred to as the molecular
Ubiquitin has two functional surfaces which are critical for various signaling processes. The hydrophobic patch (Leu8, Ile44 and Val70) is important for binding to the proteasome, UIM (ubiquitin interacting motif) and UBA (ubiquitin associated) domains. This multifunctional surface thus influences many ubiquitination and deubiquitination reactions. The other surface defined by Phe4 is required specifically for non-proteasome-dependent functions such as endocytosis and internalization, which often involves mono-ubiquitination. It is thought that Phe4 may be involved in specific protein-protein interactions that facilitate endocytosis. In addition, Ile44 forms a di-leucine signal with Leu43 that may be involved in mediating endocytosis of substrate proteins that are mono-ubiquitinated. Ubiquitin F4A can form an E1-catalyzed active thioester at the C-terminus allowing the molecule to be transferred to the lysines of substrate proteins.. ...
Most proteins in cells undergo post-translational modifications giving them structural and functional diversity for diverse roles in biological processes. Experimental identification and validation of posttranslational modifications (PTMs) is labor-intensive task and can be expensive in the absence of prior knowledge concerning PTMs. Analyzing the ubiquitome is one of the most exciting and challenging tasks in current proteomics research. A lack of curated datasets of ubiquitinated proteins presents the ultimate limiting factor in studying substrate selection mechanism in ubiquitination making it difficult to evaluate, and compare target sites. As more and more ligases are identified there exists an urgent need to rapidly and precisely identify enzyme-specific substrates to decode their selectivity and specificity [8]. Computational prediction of PTM sites has provided researchers with information on the high probability PTM sites for further experimental characterizations like PHOSIDA and ...
Study Rationale: Parkinsons disease (PD) involves accumulation of toxic proteins in cells in specific areas of the brain. These cells normally have protective mechanisms to remove these toxic proteins and dysfunction of these mechanisms may play a role in the development of PD. A major goal of this grant is to explore novel ways to allow these cells to restore their ability to remove these toxic proteins.Hypothesis:Key members of the deubiquitinase (DUB) family of enzymes are thought to play a central role in the development and progression of PD by allowing the build-up of toxic proteins. This study will determine if inhibitors of these enzymes can prevent or halt the progression of PD. Study Design:The grant recipients have expertise in the identification of drugs that block the action of DUBs. The team will apply this expertise to DUB family members that are thought to play a central role in the development and progression of PD to find new drugs. Once candidate drugs are identified, the team will
Ubiquitination of AF-6 in COS7 cells.AF-6 and HA-tagged ubiquitin (HA-Ub) were expressed in COS7 cells. COS7 cells were treated with or without 25 μM ALLN for
Different modes of ubiquitination lead to different substrate fates. The versatility of Ub in regulating different processes is derived from its ability to be c
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Wolfgang Hoehenwarter, Justin Lee, Marco Trujillo* (2017) Dampening of the Immune Response by Changes in PUB22 Ubiquitination Modes Triggered by MPK3. The Plant Cell, 29:726-745 • Giulia Furlan, Marco Trujillo* (2016) In vitro ubiquitination activity assays in plant immune responses. Plant Pattern ...
In this issue of The EMBO Journal, a multi‐layered global proteome resource, which comprehensively covers TNF‐induced phosphorylation and ubiquitination events as well as receptor interactions, has led to identification of SPATA2 as a novel player that contributes to TNF signalling by interacting with the LUBAC ubiquitin ligase and the CYLD deubiquitylase. Loss of SPATA2 augments transcriptional activation of NF‐κB and limits TNF‐induced necroptosis. A separate screen published in EMBO Reports corroborates these findings by showing that SPATA2 deficiency regulates CYLD activity, TNF‐induced NF‐κB signalling and cell death.. See also: SA Wagner et al (September 2016) and. L Schlicher et al ...
It should be noted that although we interpret the observed Bre1 knockdown phenotype as arising from an impact on the well-known role of Bre1 in H2B ubiquitination, it is formally possible that additional targets for the Bre1 ubiquitin ligase exist, which could contribute to the knockdown phenotype. Testing this with an H2B K120 substitution mutant is not straightforward in mammals because their genomes contain at least 17 H2B genes (43). However, studies using overexpressed ectopic H2BK120R mutant gene in cells with wild-type chromosomal copies of H2B have shown that effects of overexpression of H2BK120R mimic those of loss of BRE1, including the effect on the formation of γH2AX foci, which we used in our study to detect DSBs (11, 12). Also, in Saccharomyces, in which chromosomal copies of the H2B gene number only 2 and can be deleted, H2BK123R mutants do mimic the bre1 deletion phenotype (reviewed in ref. 9), implying that the phenotypes are likely to be conferred through effects on the H2B ...
Elektronische Hochschulschriften; Titel: Phosphorylation of the E3 ubiquitin ligase PUB22 controls its ubiquitination activity to dampen the immune response, Verfasser: Furlan, Giulia, Halle, [2017?]
E3 ligase Ligand 10 is a ligand for E3 ubiquitin ligase. E3 ligase Ligand 10 can be connected to the ligand for protein by a linker to form PROTACs. PROTACs are inducers of ubiquitination-mediated degradation of cancer-promoting proteins ...
G protein coupled receptors (GPCRs) constitute the largest cell-surface receptor family and at least 35% of currently prescribed drugs act on these receptor mol...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Alzheimers disease (AD) is the most common cause of dementia, affecting an estimated 5.3 million individuals in the US alone. However, the underlying cellular...
Akimov V, et al. (2018) UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites. Nat Struct Mol Biol 25, 631-640 ...
Akimov V, et al. (2018) UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites. Nat Struct Mol Biol 25, 631-640 ...
IMBB researchers contribute to the unraveling of the molecular mechanism of Notch signalling. Daskalaki et al show that ubiquitylation of th...
This gene encodes a component of the ribosome quality control complex. The encoded protein facilitates the recognition and ubiquitination of stalled 60S subunits by the ubiquitin ligase listerin. A similar protein in fly functions as a tumor suppressor. [provided by RefSeq, Jul 2016] ...
Nucleolar sequestration of RelA is an important mechanism for regulating NF-κB transcriptional activity. COMMD1(MURR1) facilitated ubiquitination acts as a critical nucleolar targeting signal for RelA, but how this ubiquitination is regulated, and how it differs from cytokine-mediated ubiquitination which causes proteasomal degradation of RelA, is poorly understood. Here we report a novel role for p300 in controlling stimulus specific ubiquitination of RelA, through modulation of COMMD1. We show that p300 is required for stress-mediated ubiquitination and nucleolar translocation of RelA, but that this effect is indirect. We also demonstrate that COMMD1 is acetylated by p300 and that acetylation protects COMMD1 from XIAP-mediated proteosomal degradation. Furthermore, we demonstrate that COMMD1 acetylation is enhanced by aspirin-mediated stress, and that this acetylation is absolutely required for the protein to bind RelA under these conditions. In contrast, TNF has no effect on COMMD1 ...
Here, we demonstrate that HOIL-1L is specifically required for NLRP3 inflammasome-dependent IL-1β secretion in BMDMs independently of NF-κB activation. Mechanistically, the assembly of the NLRP3/ASC inflammasome and linear ubiquitination of the novel LUBAC substrate, ASC, both require HOIL-1L expression. The loss of these functions in HOIL-1L−/− mice results in resistance to MDP-induced peritonitis and contributes to survival upon LPS-induced systemic inflammation. This is the first demonstration that linear ubiquitination is required for NLRP3/ASC-dependent inflammasome activation, thus expanding the role of LUBAC as an innate immune regulator. This work is also the first to compare the role of HOIL-1L in MEF and macrophage cells. Our data indicate that HOIL-1L is critical for NF-κB activation in MEF cells, consistent with the literature (Fig. 1; Tokunaga et al., 2009; Gerlach et al., 2011; Ikeda et al., 2011). However, this activity is cell type specific because HOIL-1L is not required ...