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Ubiquitination

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https://www.readbyqxmd.com/read/27915047/physical-and-functional-interaction-of-snapin-with-cav1-3-calcium-channel-impacts-channel-protein-trafficking-in-atrial-myocytes
#1
Xiao-Li Sun, Ju-Fang Yuan, Tao Jin, Xiao-Qing Cheng, Qiang Wang, Jia Guo, Wei Zhang, Yin Zhang, Ling Lu, Zhao Zhang
The L-type Ca(2+) channel (LTCC) Cav1.3 playsa critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both theheterologous expression system and mouse atrial myocytes...
November 30, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27914808/influenza-a-virus-ns1-protein-induced-a20-contributes-to-viral-replication-by-suppressing-interferon-induced-antiviral-response
#2
Wenjing Feng, Xiaoning Sun, Ning Shi, Maolin Zhang, Zhenhong Guan, Ming Duan
The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. A20 is a cytoplasmic ubiquitin-editing protein that negatively regulates the retinoic acid-inducible gene I (RIG-I)-mediated activation of interferon regulatory factors (IRF) 3. Here, we found that influenza A virus (IAV) non-structural protein (NS) 1 dramatically induced the protein level of A20 in A549 cells whose expression levels were positively associated with the viral virulence...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#3
REVIEW
Si-Fa Gao, Bo Zhong, Dandan Lin
CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27913948/branched-chain-amino-acids-administration-suppresses-endurance-exercise-related-activation-of-ubiquitin-proteasome-signaling-in-trained-human-skeletal-muscle
#4
Evgeny A Lysenko, Tatiana F Vepkhvadze, Egor M Lednev, Olga L Vinogradova, Daniil V Popov
We tested whether post exercise ingestion of branched-chain amino acids (BCAA < 10 g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1 g/kg). Post exercise ACC(Ser79/222) phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P < 0...
December 3, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27913740/a-%C3%AE-ketoacyl-coa-synthase-is-involved-in-rice-leaf-cuticular-wax-synthesis-and-requires-a-cer2-like-protein-as-a-cofactor
#5
Xiaochen Wang, Yuanyuan Guan, Du Zhang, Xiangbai Dong, Lihong Tian, Le Qing Qu
Cuticular waxes are complex mixtures of very-long-chain fatty acids (VLCFAs) and their derivatives, forming a natural barrier on aerial surfaces of terrestrial plants against biotic and abiotic stresses. In VLCFA biosynthesis, β-ketoacyl-CoA synthase (KCS) is the key enzyme, catalyzing the first reaction in fatty acid elongation and determining substrate specificity. We isolated a rice (Oryza sativa L.) wax crystal-sparse leaf 4 (WSL4) gene using a map-based cloning strategy. WSL4 is predicted to encode a KCS, a homolog of Arabidopsis CER6...
December 2, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27913667/molecular-basis-for-specificity-of-the-met1-linked-polyubiquitin-signal
#6
REVIEW
Paul R Elliott
The post-translational modification of proteins provides a rapid and versatile system for regulating all signalling pathways. Protein ubiquitination is one such type of post-translational modification involved in controlling numerous cellular processes. The unique ability of ubiquitin to form polyubiquitin chains creates a highly complex code responsible for different subsequent signalling outcomes. Specialised enzymes ('writers') generate the ubiquitin code, whereas other enzymes ('erasers') disassemble it...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913284/cardiac-proteasome-functional-insufficiency-plays-a-pathogenic-role-in-diabetic-cardiomyopathy
#7
Jie Li, Wenxia Ma, Guihua Yue, Yaoliang Tang, Il-Man Kim, Neal L Weintraub, Xuejun Wang, Huabo Su
BACKGROUND: Diabetic cardiomyopathy is a major risk factor in diabetic patients but its pathogenesis remains poorly understood. The ubiquitin-proteasome system (UPS) facilitates protein quality control by degrading unnecessary and damaged proteins in eukaryotic cells, and dysfunction of UPS is implicated in various cardiac diseases. However, the overall functional status of the UPS and its pathophysiological role in diabetic cardiomyopathy have not been determined. METHODS AND RESULTS: Type I diabetes was induced in wild-type and transgenic mice expressing a UPS functional reporter (GFPdgn) by injections of streptozotocin (STZ)...
November 29, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27913212/vcp-cooperates-with-ubxd1-to-degrade-mitochondrial-outer-membrane-protein-mcl1-in-model-of-huntington-s-disease
#8
Xing Guo, Xin Qi
Proteasome-dependent turnover of mitochondrial outer membrane (OMM)-associated proteins is one of the mechanisms for maintaining proper mitochondrial quality and function. However, the underlying pathways and their implications in human disease are poorly understood. Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by expanded CAG repeats in the N terminal of the huntingtin gene (mutant Huntingtin, mtHtt). In this study, we show an extensive degradation of the OMM protein MCL1 (Myeloid cell leukemia sequence 1) in both HD mouse striatal cells and HD patient fibroblasts...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912080/the-itch-ubiquitin-ligase-is-required-for-kshv-rta-induced-vflip-degradation
#9
Jennifer C Chmura, Kevin Herold, Ayana Ruffin, Trudymae Atuobi, Yetunde Fabiyi, Ashley E Mitchell, Young Bong Choi, Elana S Ehrlich
Expression of Kaposi's sarcoma herpesvirus vFLIP, a potent activator of NFkB signaling, promotes latency. Inhibition of NFkB signaling promotes lytic reactivation. We previously reported that lytic inducer, RTA, inhibits vFLIP induced NFkB signaling by inducing the degradation of vFLIP via the proteasome. Here we report that the cellular ubiquitin ligase, Itch, is required for RTA induced degradation of vFLIP. Expression of either Itch targeting shRNA or a dominant negative mutant of the ubiquitin ligase both increased the stability of vFLIP in the presence of RTA...
November 29, 2016: Virology
https://www.readbyqxmd.com/read/27912065/phosphoribosylation-of-ubiquitin-promotes-serine-ubiquitination-and-impairs-conventional-ubiquitination
#10
Sagar Bhogaraju, Sissy Kalayil, Yaobin Liu, Florian Bonn, Thomas Colby, Ivan Matic, Ivan Dikic
Conventional ubiquitination involves the ATP-dependent formation of amide bonds between the ubiquitin C terminus and primary amines in substrate proteins. Recently, SdeA, an effector protein of pathogenic Legionella pneumophila, was shown to mediate NAD-dependent and ATP-independent ubiquitin transfer to host proteins. Here, we identify a phosphodiesterase domain in SdeA that efficiently catalyzes phosphoribosylation of ubiquitin on a specific arginine via an ADP-ribose-ubiquitin intermediate. SdeA also catalyzes a chemically and structurally distinct type of substrate ubiquitination by conjugating phosphoribosylated ubiquitin to serine residues of protein substrates via a phosphodiester bond...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911708/regulation-of-primary-cilia-formation-by-the-ubiquitin-proteasome-system
#11
REVIEW
Robert F Shearer, Darren N Saunders
Primary cilia form at the surface of most vertebrate cell types, where they are essential signalling antennae for signal transduction pathways important for development and cancer, including Hedgehog. The importance of primary cilia in development is clearly demonstrated by numerous disorders (known as ciliopathies) associated with disrupted cilia formation (ciliogenesis). Recent advances describing functional regulators of the primary cilium highlight an emerging role for the ubiquitin-proteasome system (UPS) as a key regulator of ciliogenesis...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911343/pink1-parkin-and-mitochondrial-quality-control-what-can-we-learn-about-parkinson-s-disease-pathobiology
#12
Dominika Truban, Xu Hou, Thomas R Caulfield, Fabienne C Fiesel, Wolfdieter Springer
The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27910910/genome-wide-characterisation-and-expression-profile-of-the-grapevine-atl-ubiquitin-ligase-family-reveal-biotic-and-abiotic-stress-responsive-and-development-related-members
#13
Pietro Ariani, Alice Regaiolo, Arianna Lovato, Alejandro Giorgetti, Andrea Porceddu, Salvatore Camiolo, Darren Wong, Simone Castellarin, Elodie Vandelle, Annalisa Polverari
The Arabidopsis Tóxicos en Levadura (ATL) protein family is a class of E3 ubiquitin ligases with a characteristic RING-H2 Zn-finger structure that mediates diverse physiological processes and stress responses in plants. We carried out a genome-wide survey of grapevine (Vitis vinifera L.) ATL genes and retrieved 96 sequences containing the canonical ATL RING-H2 domain. We analysed their genomic organisation, gene structure and evolution, protein domains and phylogenetic relationships. Clustering revealed several clades, as already reported in Arabidopsis thaliana and rice (Oryza sativa), with an expanded subgroup of grapevine-specific genes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910872/sag-rbx2-e3-ligase-complexes-with-ubch10-and-ube2s-e2s-to-ubiquitylate-%C3%AE-trcp1-via-k11-linkage-for-degradation
#14
Peng Kuang, Mingjia Tan, Weihua Zhou, Qiang Zhang, Yi Sun
SAG/RBX2 and RBX1 are two family members of RING components of Cullin-RING ligases (CRLs), required for their enzymatic activity. Previous studies showed that SAG prefers to bind with CUL5, as well as CUL1, whereas RBX1 binds exclusively to CULs1-4. Detailed biochemical difference between SAG and RBX1, and whether SAG mediates cross-talk between CRL5 and CRL1 are previously unknown. Here we report that the levels of SAG and β-TrCP1 are inversely correlated, and SAG-CUL5-βTrCP1 forms a complex under physiological condition...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909314/controlled-detonation-evolution-of-necroptosis-in-pathogen-defense
#15
REVIEW
Michelle Brault, Andrew Oberst
Necroptosis is a lytic form of programmed cell death that involves the swelling and rupture of dying cells. While several necroptosis-inducing stimuli have been defined, in most cells this pathway is kept in check by the action of the pro-apoptotic protease caspase-8 and the IAP ubiquitin ligases. How and when necroptosis is triggered under physiological conditions therefore remains a persistent question. Because necroptosis likely arose as a defensive mechanism against viral infection, exploration of this question requires a consideration of host-pathogen interactions, and how the sensing of infection could sensitize cells to necroptosis...
December 2, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27909242/beneficial-effects-of-rapamycin-in-a-drosophila-model-for-hereditary-spastic-paraplegia
#16
Shiyu Xu, Michael Stern, James A McNew
The locomotor deficits in the hereditary spastic paraplegias (HSPs) reflect degeneration of upper motor neurons, but the mechanisms underlying this neurodegeneration are unknown. We established a Drosophila model for the HSP atlastin (atl), which encodes an ER fusion protein. Here we show that neuronal atl loss causes degeneration of specific thoracic muscles that is preceded by other pathologies including accumulation of aggregates containing poly-ubiquitin (poly-UB), increased generation of reactive oxygen species, and activation of the JNK/Foxo stress response pathway...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27909234/a-high-throughput-screening-strategy-for-development-of-rnf8-ubc13-protein-protein-interaction-inhibitors
#17
Elisabeth Weber, Ina Rothenaigner, Stefanie Brandner, Kamyar Hadian, Kenji Schorpp
The ubiquitin-proteasome system plays an essential role in a broad range of cellular signaling pathways. Ubiquitination is a posttranslational protein modification that involves the action of an enzymatic cascade (E1, E2, and E3 enzymes) for the covalent attachment of ubiquitin to target proteins. The emerging knowledge of the molecular mechanisms and correlation of deregulation of the ubiquitin system in human diseases is uncovering new opportunities for therapeutics development. The E3 ligase RNF8 acts in cooperation with the heterodimeric E2 enzyme Ubc13/Uev1a to generate ubiquitin conjugates at the sides of DNA double-strand breaks, and recent findings suggest RNF8 as a potential therapeutic target for the treatment of breast cancer...
December 1, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27909045/a-subset-of-ubiquitin-conjugating-enzymes-are-essential-for-plant-immunity
#18
Bangjun Zhou, Ravi V Mural, Xuanyang Chen, Matt E Oates, Richard A Connor, Gregory B Martin, Julian Gough, Lirong Zeng
Of the three classes of enzymes involved in ubiquitination, ubiquitin-conjugating enzymes (E2) have been often incorrectly considered to play merely an auxiliary role in the process and few E2 enzymes have been investigated in plants. To reveal the role of E2 in plant innate immunity we identified and cloned forty tomato genes encoding E2 proteins. Thioester assays indicated the majority of the genes encode enzymatically active E2. Phylogenetic analysis classified the forty tomato E2 into thirteen groups, of which members of group III were found to interact and act specifically with AvrPtoB, a Pseudomonas syringae pv...
December 1, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27908864/identification-of-candidate-genes-in-osteoporosis-by-integrated-microarray-analysis
#19
J J Li, B Q Wang, Q Fei, Y Yang, D Li
OBJECTIVES: In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. METHODS: We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls...
December 2016: Bone & Joint Research
https://www.readbyqxmd.com/read/27908682/tribbles-in-the-21st-century-the-evolving-roles-of-tribbles-pseudokinases-in-biology-and-disease
#20
REVIEW
Patrick A Eyers, Karen Keeshan, Natarajan Kannan
The Tribbles (TRIB) pseudokinases control multiple aspects of eukaryotic cell biology and evolved unique features distinguishing them from all other protein kinases. The atypical pseudokinase domain retains a regulated binding platform for substrates, which are ubiquitinated by context-specific E3 ligases. This plastic configuration has also been exploited as a scaffold to support the modulation of canonical MAPK and AKT modules. In this review, we discuss the evolution of TRIBs and their roles in vertebrate cell biology...
November 28, 2016: Trends in Cell Biology
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