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Trim5o Requires Ube2w to Anchor Lys63-Linked Ubiquitin Chains And
Article TRIM5a requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription Adam J Fletcher1,†,§, Devin E Christensen2,§, Chad Nelson2, Choon Ping Tan1, Torsten Schaller1,‡, Paul J Lehner3, Wesley I Sundquist2 & Greg J Towers1,* Abstract followed by variable protein interaction domain(s). Although TRIM proteins can have wide-ranging biological roles, anti-pathogen TRIM5a is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that defense functions are common (Nisole et al, 2005; McNab et al, assembles on incoming retroviral capsids and induces their prema- 2011). The expression of many TRIM proteins is induced by type I ture dissociation. It inhibits reverse transcription of the viral interferons, and several have been shown to manipulate immune genome and can also synthesize unanchored polyubiquitin (poly- signaling pathways by ubiquitinating signal transducing proteins, Ub) chains to stimulate innate immune responses. Here, we show such as TRIM23, TRIM25, and TRIM56 (Gack et al, 2007; Arimoto that TRIM5a employs the E2 Ub-conjugating enzyme Ube2Wto et al, 2010; Tsuchida et al, 2010). Certain TRIM proteins, including anchor the Lys63-linked polyUb chains in a process of TRIM5a TRIM5a (Stremlau et al, 2004), TRIM21 (Mallery et al, 2010), and auto-ubiquitination. Chain anchoring is initiated, in cells and TRIM56 (Wang et al, 2011), have also been shown to target viral in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5a. replication specifically. An emerging theme is that antiviral TRIM This modification serves as a substrate for the elongation of proteins both inhibit viral infection and initiate innate immune anchored Lys63-linked polyUb chains, catalyzed by the heterodi- signaling cascades that lead to inflammatory cytokine production meric E2 enzyme Ube2N/Ube2V2. -
The Effect of Temperature Adaptation on the Ubiquitin–Proteasome Pathway in Notothenioid Fishes Anne E
© 2017. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2017) 220, 369-378 doi:10.1242/jeb.145946 RESEARCH ARTICLE The effect of temperature adaptation on the ubiquitin–proteasome pathway in notothenioid fishes Anne E. Todgham1,*, Timothy A. Crombie2 and Gretchen E. Hofmann3 ABSTRACT proliferation to compensate for the effects of low temperature on ’ There is an accumulating body of evidence suggesting that the sub- aerobic metabolism (Johnston, 1989; O Brien et al., 2003; zero Antarctic marine environment places physiological constraints Guderley, 2004). Recently, there has been an accumulating body – on protein homeostasis. Levels of ubiquitin (Ub)-conjugated proteins, of literature to suggest that protein homeostasis the maintenance of – 20S proteasome activity and mRNA expression of many proteins a functional protein pool has been highly impacted by evolution involved in both the Ub tagging of damaged proteins as well as the under these cold and stable conditions. different complexes of the 26S proteasome were measured to Maintaining protein homeostasis is a fundamental physiological examine whether there is thermal compensation of the Ub– process, reflecting a dynamic balance in synthetic and degradation proteasome pathway in Antarctic fishes to better understand the processes. There are numerous lines of evidence to suggest efficiency of the protein degradation machinery in polar species. Both temperature compensation of protein synthesis in Antarctic Antarctic (Trematomus bernacchii, Pagothenia borchgrevinki)and invertebrates (Whiteley et al., 1996; Marsh et al., 2001; Robertson non-Antarctic (Notothenia angustata, Bovichtus variegatus) et al., 2001; Fraser et al., 2002) and fish (Storch et al., 2005). In notothenioids were included in this study to investigate the zoarcid fishes, it has been demonstrated that Antarctic eelpouts mechanisms of cold adaptation of this pathway in polar species. -
Trim5alpha Restricts Flavivirus Replication by Targeting the Viral Protease for Proteasomal Degradation
University of Massachusetts Medical School eScholarship@UMMS Program in Molecular Medicine Publications and Presentations Program in Molecular Medicine 2019-06-11 TRIM5alpha Restricts Flavivirus Replication by Targeting the Viral Protease for Proteasomal Degradation Abhilash I. Chiramel National Institute of Allergy and Infectious Diseases Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/pmm_pp Part of the Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Enzymes and Coenzymes Commons, Immunology and Infectious Disease Commons, Molecular Biology Commons, Molecular Genetics Commons, and the Virology Commons Repository Citation Chiramel AI, Meyerson NR, McNally KL, Broeckel RM, Montoya VR, Mendez-Solis O, Robertson SJ, Sturdevant GL, Lubick KJ, Nair V, Youseff BH, Ireland RM, Bosio CM, Kim K, Luban J, Hirsch VM, Taylor RT, Bouamr F, Sawyer SL, Best SM. (2019). TRIM5alpha Restricts Flavivirus Replication by Targeting the Viral Protease for Proteasomal Degradation. Program in Molecular Medicine Publications and Presentations. https://doi.org/10.1016/j.celrep.2019.05.040. Retrieved from https://escholarship.umassmed.edu/ pmm_pp/97 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Program in Molecular Medicine Publications and Presentations by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Article TRIM5a Restricts Flavivirus Replication by Targeting the Viral Protease for Proteasomal Degradation Graphical Abstract Authors Abhilash I. Chiramel, Nicholas R. Meyerson, Kristin L. McNally, ..., Fadila Bouamr, Sara L. -
Implication of Trim5alpha and Trimcyp in Interferon-Induced Anti
Implication of TRIM5alpha and TRIMCyp in interferon-induced anti-retroviral restriction activities Laëtitia Carthagéna, Mélanie Parise, Mathieu Ringeard, Mounira Chelbi-Alix, Uriel Hazan, Sébastien Nisole To cite this version: Laëtitia Carthagéna, Mélanie Parise, Mathieu Ringeard, Mounira Chelbi-Alix, Uriel Hazan, et al.. Implication of TRIM5alpha and TRIMCyp in interferon-induced anti-retroviral restriction activities. Retrovirology, BioMed Central, 2008, 5 (1), pp.59. 10.1186/1742-4690-5-59. hal-02503964 HAL Id: hal-02503964 https://hal.archives-ouvertes.fr/hal-02503964 Submitted on 10 Mar 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Retrovirology BioMed Central Research Open Access Implication of TRIMalpha and TRIMCyp in interferon-induced anti-retroviral restriction activities Laetitia Carthagena1,2, Mélanie C Parise1,2, Mathieu Ringeard1,2, Mounira K Chelbi-Alix3, Uriel Hazan1,2,4 and Sébastien Nisole*1,2,4 Address: 1Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Département des Maladies Infectieuses, 22 rue Méchain, 75014, -
Identification of the Binding Partners for Hspb2 and Cryab Reveals
Brigham Young University BYU ScholarsArchive Theses and Dissertations 2013-12-12 Identification of the Binding arP tners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non- Redundant Roles for Small Heat Shock Proteins Kelsey Murphey Langston Brigham Young University - Provo Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Microbiology Commons BYU ScholarsArchive Citation Langston, Kelsey Murphey, "Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins" (2013). Theses and Dissertations. 3822. https://scholarsarchive.byu.edu/etd/3822 This Thesis is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston A thesis submitted to the faculty of Brigham Young University in partial fulfillment of the requirements for the degree of Master of Science Julianne H. Grose, Chair William R. McCleary Brian Poole Department of Microbiology and Molecular Biology Brigham Young University December 2013 Copyright © 2013 Kelsey Langston All Rights Reserved ABSTRACT Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactors and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston Department of Microbiology and Molecular Biology, BYU Master of Science Small Heat Shock Proteins (sHSP) are molecular chaperones that play protective roles in cell survival and have been shown to possess chaperone activity. -
Open Source Web GUI Toolkits
Open Source Web GUI Toolkits "A broad and probably far too shallow presentation on stuff that will probably change 180 degrees by the time you hear about it from me" Nathan Schlehlein [email protected] 1 Why Web Developers Drink... Can't get away with knowing one thing A Fairly Typical Web App... ➔ MySQL – Data storage ➔ PHP – Business logic ➔ Javascript - Interactivity ➔ HTML – Presentation stuff ➔ CSS – Presentation formatting stuff ➔ Images – They are... Purdy... ➔ httpd.conf, php.ini, etc. Problems are liable to pop up at any stage... 2 The Worst Thing. Ever. Browser Incompatibilities! Follow the rules, still lose Which is right? ➔ Who cares! You gotta make it work anyways! Solutions More work or less features? ➔ Use browser-specific stuff - Switch via Javascript ➔ Use a subset of HTML that most everyone agrees on 3 Web Application? Web sites are... OK, but... Boring... Bounce users from page to page Stuff gets messed up easily ➔ Bookmarks? Scary... ➔ Back button 4 Why A Web Toolkit? Pros: Let something else worry about difficult things ➔ Layout issues ➔ Session management ➔ Browser cross-compatibility ➔ Annoying RPC stuff 5 >INSERT BUZZWORD HERE< Neat web stuff has been happening lately... AJAX “Web 2.0” Google maps Desktop app characteristics on the web... 6 Problem With >BUZZWORDS< Nice, but... Lots of flux ➔ Technology ➔ Expectations of technology Communications can get tricky Yet another thing to program... ➔ (Correctly) 7 Why A Web Toolkit? Pros: Let something else worry about difficult things ➔ Communications management ➔ Tested Javascript code ➔ Toolkit deals with changes, not the programmer 8 My Criteria Bonuses For... A familiar programming language ➔ Javascript? Unit test capability ➔ Test early, test often, sleep at night Ability to incrementally introduce toolkit Compatibility with existing application Documentation Compelling Examples 9 Web Toolkits – Common Features ■ Widgets ■ Layouts ■ Manipulation of page elements DOM access, etc. -
A Drosophila Ortholog of the Human Cylindromatosis Tumor Suppressor
RESEARCH ARTICLE 2605 Development 134, 2605-2614 (2007) doi:10.1242/dev.02859 A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense Theodore Tsichritzis1, Peer C. Gaentzsch3, Stylianos Kosmidis2, Anthony E. Brown3, Efthimios M. Skoulakis2, Petros Ligoxygakis3,* and George Mosialos1,4,* The cylindromatosis (CYLD) gene is mutated in human tumors of skin appendages. It encodes a deubiquitylating enzyme (CYLD) that is a negative regulator of the NF-B and JNK signaling pathways, in vitro. However, the tissue-specific function and regulation of CYLD in vivo are poorly understood. We established a genetically tractable animal model to initiate a systematic investigation of these issues by characterizing an ortholog of CYLD in Drosophila. Drosophila CYLD is broadly expressed during development and, in adult animals, is localized in the fat body, ovaries, testes, digestive tract and specific areas of the nervous system. We demonstrate that the protein product of Drosophila CYLD (CYLD), like its mammalian counterpart, is a deubiquitylating enzyme. Impairment of CYLD expression is associated with altered fat body morphology in adult flies, increased triglyceride levels and increased survival under starvation conditions. Furthermore, flies with compromised CYLD expression exhibited reduced resistance to bacterial infections. All mutant phenotypes described were reversible upon conditional expression of CYLD transgenes. Our results implicate CYLD in a broad range of functions associated with fat homeostasis and host defence in Drosophila. KEY WORDS: Cylindromatosis, Drosophila, Fat body, Host defense, NF-kappaB INTRODUCTION disease and it is required for the proper development of T Familial cylindromatosis is an autosomal-dominant predisposition lymphocytes in mice (Costello et al., 2005; Reiley et al., 2006). -
Defining Functional Interactions During Biogenesis of Epithelial Junctions
ARTICLE Received 11 Dec 2015 | Accepted 13 Oct 2016 | Published 6 Dec 2016 | Updated 5 Jan 2017 DOI: 10.1038/ncomms13542 OPEN Defining functional interactions during biogenesis of epithelial junctions J.C. Erasmus1,*, S. Bruche1,*,w, L. Pizarro1,2,*, N. Maimari1,3,*, T. Poggioli1,w, C. Tomlinson4,J.Lees5, I. Zalivina1,w, A. Wheeler1,w, A. Alberts6, A. Russo2 & V.M.M. Braga1 In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. 1 National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. 2 Computing Department, Imperial College London, London SW7 2AZ, UK. 3 Bioengineering Department, Faculty of Engineering, Imperial College London, London SW7 2AZ, UK. 4 Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Cytosolic Fc Receptor TRIM21 Inhibits Seeded Tau Aggregation
Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation William A. McEwana,1, Benjamin Falcona, Marina Vaysburda, Dean Clifta, Adrian L. Oblakb, Bernardino Ghettib, Michel Goederta,1, and Leo C. Jamesa,1 aMedical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; and bDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 Edited by Alexander Espinosa, Karolinska Institutet, Stockholm, Sweden, and accepted by Editorial Board Member Stephen P. Goff December 6, 2016 (received for review May 6, 2016) Alzheimer’s disease (AD) and other neurodegenerative disorders assemblies into the brains of tau transgenic mice promotes the are associated with the cytoplasmic aggregation of microtubule- aggregation of intracellular tau (7), and ectopic addition of associated protein tau. Recent evidence supports transcellular recombinant tau assemblies promotes the aggregation of in- transfer of tau misfolding (seeding) as the mechanism of spread tracellular pools in cultured cells (8, 9). Consistent with trans- within an affected brain, a process reminiscent of viral infection. cellular propagation of misfolding, tau pathology in AD spreads However, whereas microbial pathogens can be recognized as non- between connected regions of the brain in a stereotyped manner self by immune receptors, misfolded protein assemblies evade detec- (10). Seeded propagation of misfolded tau is therefore proposed tion, as they are host-derived. Here, we show that when misfolded to underlie many common neurodegenerative disorders. Akin to tau assemblies enter the cell, they can be detected and neutralized via viral infection, this model of seeded tau propagation relies on the a danger response mediated by tau-associated antibodies and the physical transfer of tau assemblies between cells, and is therefore cytosolic Fc receptor tripartite motif protein 21 (TRIM21). -
Material Data Sheet
MATERIAL DATA SHEET Recombinant Human His6 UBE2N/UBE2V2 Complex Cat. # E2666 Ubiquitin conjugating Enzyme E2N (UBE2N), also known as Ubiquitin conjugating Enzyme 13 (Ubc13), forms a functional complex with the catalytically inactive UBE2V2 (human homologue of yeast MMS2) protein (1). Human UBE2N/Ubc13 shares 100% and 99% amino acid (aa) sequence identity with the mouse and rat orthologs, respectively, while human UBE2V2 shares 99% aa sequence identity with its mouse and rat orthologs. The UBE2N/UBE2V2 Complex functions with Ubiquitin ligases (E3s), including RNF111 and RNF8, to synthesize Lys63linked Ubiquitin chains (2,3) that can either be unanchored or attached to target proteins (4, 5). The UBE2N/UBE2V2 complex has important roles in facilitating responses to various forms of DNA damage (2, 6). Product Information Quantity: 100 µg | 50 µg MW: 18 kDa (UBE2N), 17 kDa (UBE2V2) Source: E. coliderived Contains an Nterminal 6His tag Accession # P61088 (UBE2N)/Q15819 (UBE2V2) Stock: 0.88 mg/ml (25 μM) in 50 mM HEPES pH 7.5, 200 mM NaCl, 10% Glycerol (v/v), 2 mM TCEP Purity: >95%, by SDSPAGE under reducing conditions and visualized by Colloidal Coomassie® Blue stain. Rev. 5/22/2014 Page 1 of 2 www.bostonbiochem.com Boston Biochem products are available via the R&D Systems distributor network. USA & CANADA Tel: (800) 343-7475 EUROPE Tel: +44 (0)1235 529449 CHINA Tel: +86 (21) 52380373 Use & Storage Use: Recombinant Human His6UBE2N/UBE2V2 Complex is a member of the Ubiquitin conjugating (E2) enzyme family that receives Ubiquitin from a Ubiquitin activating (E1) enzyme and subsequently interacts with a Ubiquitin ligase (E3) to conjugate Ubiquitin to substrate proteins. -
UBE2E1 (Ubch6) [Untagged] E2 – Ubiquitin Conjugating Enzyme
UBE2E1 (UbcH6) [untagged] E2 – Ubiquitin Conjugating Enzyme Alternate Names: UbcH6, UbcH6, Ubiquitin conjugating enzyme UbcH6 Cat. No. 62-0019-100 Quantity: 100 µg Lot. No. 1462 Storage: -70˚C FOR RESEARCH USE ONLY NOT FOR USE IN HUMANS CERTIFICATE OF ANALYSIS Page 1 of 2 Background Physical Characteristics The enzymes of the ubiquitylation Species: human Protein Sequence: pathway play a pivotal role in a num- GPLGSPGIPGSTRAAAM SDDDSRAST ber of cellular processes including Source: E. coli expression SSSSSSSSNQQTEKETNTPKKKESKVSMSKN regulated and targeted proteasomal SKLLSTSAKRIQKELADITLDPPPNCSAGP degradation of substrate proteins. Quantity: 100 μg KGDNIYEWRSTILGPPGSVYEGGVFFLDIT FTPEYPFKPPKVTFRTRIYHCNINSQGVI Three classes of enzymes are in- Concentration: 1 mg/ml CLDILKDNWSPALTISKVLLSICSLLTDCNPAD volved in the process of ubiquitylation; PLVGSIATQYMTNRAEHDRMARQWTKRYAT activating enzymes (E1s), conjugating Formulation: 50 mM HEPES pH 7.5, enzymes (E2s) and protein ligases 150 mM sodium chloride, 2 mM The residues underlined remain after cleavage and removal (E3s). UBE2E1 is a member of the E2 dithiothreitol, 10% glycerol of the purification tag. ubiquitin-conjugating enzyme family UBE2E1 (regular text): Start bold italics (amino acid and cloning of the human gene was Molecular Weight: ~23 kDa residues 1-193) Accession number: AAH09139 first described by Nuber et al. (1996). UBE2E1 shares 74% sequence ho- Purity: >98% by InstantBlue™ SDS-PAGE mology with UBE2D1 and contains an Stability/Storage: 12 months at -70˚C; N-terminal extension of approximately aliquot as required 40 amino acids. A tumour suppressor candidate, tumour-suppressing sub- chromosomal transferable fragment Quality Assurance cDNA (TSSC5) is located in the re- gion of human chromosome 11p15.5 Purity: Protein Identification: linked with Beckwith-Wiedemann syn- 4-12% gradient SDS-PAGE Confirmed by mass spectrometry.