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https://www.readbyqxmd.com/read/30315202/genetic-interactions-between-aba-signalling-and-the-arg-n-end-rule-pathway-during-arabidopsis-seedling-establishment
#1
Hongtao Zhang, Lucy Gannon, Peter D Jones, Chelsea A Rundle, Kirsty L Hassall, Daniel J Gibbs, Michael J Holdsworth, Frederica L Theodoulou
The Arg/N-end rule pathway of ubiquitin-mediated proteolysis has multiple functions throughout plant development, notably in the transition from dormant seed to photoautotrophic seedling. PROTEOLYSIS6 (PRT6), an N-recognin E3 ligase of the Arg/N-end rule regulates the degradation of transcription factor substrates belonging to Group VII of the Ethylene Response Factor superfamily (ERFVIIs). It is not known whether ERFVIIs are associated with all known functions of the Arg/N-end rule, and the downstream pathways influenced by ERFVIIs are not fully defined...
October 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30311441/yeast-transformation-efficiency-is-enhanced-by-torc1-and-eisosome-dependent-signaling
#2
Sheng-Chun Yu, Florian Kuemmel, Maria-Nefeli Skoufou-Papoutsaki, Pietro D Spanu
Transformation of baker's yeast (Saccharomyces cerevisiae) plays a key role in several experimental techniques, yet the molecular mechanisms underpinning transformation are still unclear. The addition of amino acids to the growth and transformation medium increases transformation efficiency. Here, we show that target of rapamycin complex 1 (TORC1) activated by amino acids enhances transformation via ubiquitin-mediated endocytosis. We created mutants of the TORC1 pathway, alpha-arrestins, and eisosome-related genes...
October 11, 2018: MicrobiologyOpen
https://www.readbyqxmd.com/read/30308158/a-viral-protein-restricts-drosophila-rnai-immunity-by-regulating-argonaute-activity-and-stability
#3
Arabinda Nayak, Dong Young Kim, Michael J Trnka, Craig H Kerr, Peter V Lidsky, David J Stanley, Brianna Monique Rivera, Kathy H Li, Alma L Burlingame, Eric Jan, Judith Frydman, John D Gross, Raul Andino
The dicistrovirus, Cricket paralysis virus (CrPV) encodes an RNA interference (RNAi) suppressor, 1A, which modulates viral virulence. Using the Drosophila model, we combined structural, biochemical, and virological approaches to elucidate the strategies by which CrPV-1A restricts RNAi immunity. The atomic resolution structure of CrPV-1A uncovered a flexible loop that interacts with Argonaute 2 (Ago-2), thereby inhibiting Ago-2 endonuclease-dependent immunity. Mutations disrupting Ago-2 binding attenuates viral pathogenesis in wild-type but not Ago-2-deficient flies...
October 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30295974/e3-ubiquitin-ligases-lnx1-and-lnx2-localize-at-neuronal-gap-junctions-formed-by-connexin36-in-rodent-brain-and-molecularly-interact-with-connexin36
#4
B D Lynn, Xinbo Li, S G Hormuzdi, E K Griffiths, C J McGlade, J I Nagy
Electrical synapses in the mammalian central nervous system (CNS) are increasingly recognized as highly complex structures for mediation of neuronal communication, both with respect to their capacity for dynamic short and long-term modification in efficacy of synaptic transmission and their multi-molecular regulatory and structural components. These two characteristics are inextricably linked, such that understanding of mechanisms that contribute to electrical synaptic plasticity requires knowledge of the molecular composition of electrical synapses and the functions of proteins associated with these synapses...
October 8, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/30287392/mechanisms-controlling-the-multistage-post-translational-processing-of-endogenous-nrf1%C3%AE-tcf11-proteins-to-yield-distinct-isoforms-within-the-coupled-positive-and-negative-feedback-circuits
#5
Yuancai Xiang, Meng Wang, Shaofan Hu, Lu Qiu, Fang Yang, Zhengwen Zhang, Siwang Yu, Jingbo Pi, Yiguo Zhang
To gain a better understanding of the multistep processing of Nrf1 to yield various isoforms with confused molecular masses, we herein establish a generally acceptable criterion required for identification of its endogenous full-length proteins and derivative isoforms expressed differentially in distinct experimental cell lines. Further work has been focused on the molecular mechanisms that dictate the successive post-translational modifications (i.e. glycosylation by OST, deglycosylation by NGLY, and ubiquitination by Hrd1) of this CNC-bZIP protein and its proteolytic processing to give rise to multiple proteoforms...
October 1, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/30284519/a-nutrient-cocktail-prevents-lipid-metabolism-alterations-induced-by-20-days-of-daily-steps-reduction-and-fructose-overfeeding-result-from-a-randomized-study
#6
Anthony Damiot, Rémi Demangel, John Noone, Isabelle Chery, Alexandre Zahariev, Sylvie Normand, Thomas Brioche, François Crampes, Isabelle de Glisezinski, Etienne Lefai, Marie-Pierre Bareille, Angele Chopard, Jocelyne Drai, Delphine Collin-Chavagnac, Martina Heer, Guillemette Gauquelin-Koch, Michel Prost, Patrick Simon, Guillaume Py, Stéphane Blanc, Chantal Simon, Audrey Bergouignan, Donal J O'Gorman
CONTEXT: Physical inactivity and sedentary behaviours are independent risks factors for numerous diseases. OBJECTIVE: We examined the capacity of a nutrient cocktail composed of polyphenols, omega-3 fatty acids, vitamin E and selenium to prevent the expected metabolic alterations induced physical activity and sedentary behaviors. DESIGN/SETTING/PARTICIPANTS: Twenty healthy trained men (averaging∼14,000 steps/d and engaged in sports) were randomly divided into a control group (no supplementation) and a cocktail group for a 20-day free-living intervention during which they stopped exercise and decreased their daily steps to averaging∼3000...
October 4, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/30283947/inhibition-by-microbial-metabolites-of-chinese-dark-tea-of-age-related-neurodegenerative-disorders-in-senescence-accelerated-mouse-prone-8-samp8-mice
#7
Shuxian Cai, Heng Yang, Beibei Wen, Kun Zhu, Xin Zheng, Jianan Huang, Yingzi Wang, Zhonghua Liu, Pengfei Tu
Dark tea has a significant effect on the prevention and treatment of age-related degenerative diseases. At present, further exploration of its functional mechanisms is delayed because of the complexity of post-fermentation microbial metabolites during the production phase. In this study, new isolated microbial metabolites extracted from dark tea were used to explore the neuroprotective effects, and they also helped allow further exploration of the mechanism of dark tea. Taking senescence-accelerated mouse prone 8 (SAMP8) mice as a biological model, we examined the protective effect on brain neurons of post-fermentation microbial metabolites which were extracted from dark tea...
October 4, 2018: Food & Function
https://www.readbyqxmd.com/read/30279700/sumo-targeted-ubiquitin-ligases-stubls-reduce-the-toxicity-and-abnormal-transcriptional-activity-associated-with-a-mutant-aggregation-prone-fragment-of-huntingtin
#8
Kentaro Ohkuni, Nagesh Pasupala, Jennifer Peek, Grace Lauren Holloway, Gloria D Sclar, Reuben Levy-Myers, Richard E Baker, Munira A Basrai, Oliver Kerscher
Cell viability and gene expression profiles are altered in cellular models of neurodegenerative disorders such as Huntington's Disease (HD). Using the yeast model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity associated with a mutant, aggregation-prone fragment of huntingtin (Htt), the causative agent of HD. We demonstrate that expression of an aggregation-prone Htt construct with 103 glutamine residues (103Q), but not the non-expanded form (25Q), results in severe growth defects in slx5 Δ and slx8 Δ cells...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/30266287/cyclophilin-d-deficiency-attenuates-mitochondrial-f1fo-atp-synthase-dysfunction-via-oscp-in-alzheimer-s-disease
#9
Esha Gauba, Hao Chen, Lan Guo, Heng Du
Mitochondrial dysfunction is pivotal in inducing synaptic injury and neuronal stress in Alzheimer's disease (AD). Mitochondrial F1Fo ATP synthase deregulation is a hallmark mitochondrial defect leading to oxidative phosphorylation (OXPHOS) failure in this neurological disorder. Oligomycin sensitivity conferring protein (OSCP) is a crucial F1Fo ATP synthase subunit. Decreased OSCP levels and OSCP interaction with amyloid β (Aβ) constitute key aspects of F1Fo ATP synthase pathology in AD-related conditions...
September 26, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/30264212/hip2-ubiquitin-conjugating-enzyme-has-a-role-in-uv-induced-g1-s-arrest-and-re-entry
#10
Nan Hee Hong, Yeong Jin Tak, Hyangshuk Rhim, Seongman Kang
Regulation of cell cycle arrest and re-entry triggered by DNA damage is vital for cell division and growth and is also involved in cell survival. UV radiation can generate lesions in the DNA, which results in cell cycle arrest and the induction of the DNA repair process. However, the mechanism of promoting cell cycle progression following DNA repair is elusive. The primary aim of this study is to investigate whether Hip2 ubiquitin-conjugating enzyme has a role in UV-induced G1/S arrest and re-entry. The phase of HEK293 cells was synchronized at the G1/S border using thymidine...
September 27, 2018: Genes & Genomics
https://www.readbyqxmd.com/read/30261639/-drosophila-huwe1-ubiquitin-ligase-regulates-endoreplication-and-antagonizes-jnk-signaling-during-salivary-gland-development
#11
Yifat Yanku, Eliya Bitman-Lotan, Yaniv Zohar, Estee Kurant, Norman Zilke, Martin Eilers, Amir Orian
The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, d HUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development...
September 26, 2018: Cells
https://www.readbyqxmd.com/read/30261451/ubiquitination-at-the-interface-of-tumor-viruses-and-dna-damage-responses
#12
REVIEW
Joseph M Dybas, Christin Herrmann, Matthew D Weitzman
Viruses exploit cellular ubiquitination machinery to shape the host proteome and promote productive infection. Among the cellular processes influenced by viral manipulation of ubiquitination is the DNA damage response (DDR), a network of cellular signaling pathways that sense and respond to genomic damage. This host-pathogen interaction is particularly important during virus replication and transformation by DNA tumor viruses. Manipulating DDR pathways can promote virus replication but also impacts host genomic instability, potentially leading to cellular transformation and tumor formation...
September 24, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/30261176/zinc-binding-triggers-a-conformational-switch-in-the-cullin-3-substrate-adaptor-protein-keap1-that-controls-transcription-factor-nrf2
#13
Michael McMahon, Samuel R Swift, John D Hayes
Kelch-like ECH-associated protein 1 (Keap1) is a cullin-3 (Cul3)-RING ubiquitin ligase (CRL) adaptor/scaffold protein that enables cells to adapt to environmental stressors because modification of certain of its Cys residues initiates de-repression of the NF-E2 p45-related factor-2 (Nrf2) transcription factor. Thus, in normal unstressed cells, the cytoprotective Nrf2 is continuously ubiquitylated by CRLKeap1 , thereby ensuring that Nrf2 is efficiently degraded by the proteasome and expression of Nrf2 target genes restricted...
September 24, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/30258054/a-bidentate-polycomb-repressive-deubiquitinase-complex-is-required-for-efficient-activity-on-nucleosomes
#14
Martina Foglizzo, Adam J Middleton, Abigail E Burgess, Jennifer M Crowther, Renwick C J Dobson, James M Murphy, Catherine L Day, Peter D Mace
Attachment of ubiquitin to lysine 119 of Histone 2A (H2AK119Ub) is an epigenetic mark characteristic of repressed developmental genes, which is removed by the Polycomb Repressive-Deubiquitinase (PR-DUB) complex. Here we report the crystal structure of the Drosophila PR-DUB, revealing that the deubiquitinase Calypso and its activating partner ASX form a 2:2 complex. The bidentate Calypso-ASX complex is generated by dimerisation of two activated Calypso proteins through their coiled-coil regions. Disrupting the Calypso dimer interface does not affect inherent catalytic activity, but inhibits removal of H2AK119Ub as a consequence of impaired recruitment to nucleosomes...
September 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/30257870/angelman-syndrome-associated-point-mutations-in-the-zn-binding-n-terminal-azul-domain-of-ube3a-ubiquitin-ligase-inhibit-binding-to-the-proteasome
#15
Simone Kühnle, Gustavo Martinez-Noël, Flavien Leclere, Sebastian D Hayes, J Wade Harper, Peter M Howley
Deregulation of the HECT ubiquitin ligase UBE3A/E6AP has been implicated in Angelman Syndrome as well as autism spectrum disorders (ASD). We and others have previously identified the 26S proteasome as one of the major UBE3A interacting protein complexes. Here we characterize the interaction of UBE3A and the proteasomal subunit PSMD4 (Rpn10/S5a). We map the interaction to the highly conserved N-terminal AZUL domain of UBE3A, the integrity of which is crucial for binding to PSMD4. Interestingly, two Angelman Syndrome point mutations that affect the AZUL domain show an impaired ability to bind PSMD4...
September 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30254053/substrate-binding-allosterically-relieves-autoinhibition-of-the-pseudokinase-trib1
#16
Sam A Jamieson, Zheng Ruan, Abigail E Burgess, Jack R Curry, Hamish D McMillan, Jodi L Brewster, Anita K Dunbier, Alison D Axtman, Natarajan Kannan, Peter D Mace
The Tribbles family of pseudokinases recruits substrates to the ubiquitin ligase COP1 to facilitate ubiquitylation. CCAAT/enhancer-binding protein (C/EBP) family transcription factors are crucial Tribbles substrates in adipocyte and myeloid cell development. We found that the TRIB1 pseudokinase was able to recruit various C/EBP family members and that the binding of C/EBPβ was attenuated by phosphorylation. To explain the mechanism of C/EBP recruitment, we solved the crystal structure of TRIB1 in complex with C/EBPα, which revealed that TRIB1 underwent a substantial conformational change relative to its substrate-free structure and bound C/EBPα in a pseudosubstrate-like manner...
September 25, 2018: Science Signaling
https://www.readbyqxmd.com/read/30242710/strategies-to-trap-enzyme-substrate-complexes-that-mimic-michaelis-intermediates-during-e3-mediated-ubiquitin-like-protein-ligation
#17
Frederick C Streich, Christopher D Lima
Most cellular functions rely on pathways that catalyze posttranslational modification of cellular proteins by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins. Like other posttranslational modifications that require distinct writers, readers, and erasers during signaling, Ub/Ubl pathways employ distinct enzymes that catalyze Ub/Ubl attachment, Ub/Ubl recognition, and Ub/Ubl removal. Ubl protein conjugation typically relies on parallel but distinct enzymatic cascades catalyzed by an E1-activating enzyme, an E2 carrier protein, and an E3 ubiquitin-like protein ligase...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30242705/ubiquitin-activated-interaction-traps-ubaits-tools-for-capturing-protein-protein-interactions
#18
Hazel F O'Connor, Caleb D Swaim, Larissa A Canadeo, Jon M Huibregtse
UBAITs (Ubiquitin-Activated Interaction Traps) are reagents that capitalize on the biochemistry of the ubiquitin system to covalently trap transient protein-protein interactions. UBAITs consist of an affinity-tagged protein of interest fused to a short linker followed by a C-terminal ubiquitin moiety. When charged in an E1- and E2-dependent manner, the C-terminal ubiquitin moiety of the UBAIT has the potential to form an amide linkage with lysine side chains of a protein that interacts transiently with the protein of interest, thereby covalently trapping the protein-protein interaction...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30241600/a-maldi-tof-approach-to-ubiquitin-ligase-activity
#19
Bianca D M van Tol, Paul P Geurink, Huib Ovaa
In this issue of Cell Chemical Biology,De Cesare et al. (2018) report the development of a high-throughput assay that measures E2/E3 enzyme activity by MALDI-TOF mass spectrometry and apply this to screen for small molecule E3 inhibitors. This assay potentially accelerates the drug discovery for the ubiquitin ligation pathway.
September 20, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/30239418/sepsis-increases-muscle-proteolysis-in-severely-burned-adults-but-does-not-impact-whole-body-lipid-or-carbohydrate-kinetics
#20
Andrew Murton, Fredrick J Bohanon, John O Ogunbileje, Karel D Capek, Ellen A Tran, Tony Chao, Labros S Sidossis, Craig Porter, David N Herndon
Sepsis is a common and often fatal consequence of severe burn injury, but its exact effects on whole body and muscle metabolism in the burn patient is unclear. To address this, 13 septic and 11 nonseptic patients (age: 36.9 ± 13.0 years) with burns encompassing >30% of their total body surface area underwent muscle protein kinetic studies under postabsorptive conditions using bolus injections of ring-C6 and N phenylalanine isotopes. In parallel, whole-body lipid and carbohydrate kinetics were assessed using constant infusions of [U-C6]palmitate, [6,6-H2]glucose, and [H5]glycerol, and during a 2-h hyperinsulinemic euglycemic clamp...
September 19, 2018: Shock
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