Potential Microrna-Related Targets in Clearance Pathways of Amyloid-Β
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UBE2D3 Antibody Order 021-34695924 [email protected] Support 400-6123-828 50Ul [email protected] 100 Ul √ √ Web
TD2261 UBE2D3 Antibody Order 021-34695924 [email protected] Support 400-6123-828 50ul [email protected] 100 uL √ √ Web www.ab-mart.com.cn Description: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys- 22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction. -
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. -
LRP2 Is Associated with Plasma Lipid Levels 311 Original Article
310 Journal of Atherosclerosis and Thrombosis Vol.14, No.6 LRP2 is Associated with Plasma Lipid Levels 311 Original Article Genetic Association of Low-Density Lipoprotein Receptor-Related Protein 2 (LRP2) with Plasma Lipid Levels Akiko Mii1, 2, Toshiaki Nakajima2, Yuko Fujita1, Yasuhiko Iino1, Kouhei Kamimura3, Hideaki Bujo4, Yasushi Saito5, Mitsuru Emi2, and Yasuo Katayama1 1Department of Internal Medicine, Divisions of Neurology, Nephrology, and Rheumatology, Nippon Medical School, Tokyo, Japan. 2Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, Kawasaki, Japan. 3Awa Medical Association Hospital, Chiba, Japan. 4Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba, Japan. 5Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan. Aim: Not all genetic factors predisposing phenotypic features of dyslipidemia have been identified. We studied the association between the low density lipoprotein-related protein 2 gene (LRP2) and levels of plasma total cholesterol (T-Cho) and LDL-cholesterol (LDL-C) among 352 adults in Japan. Methods: Subjects were obtained from among participants in a cohort study that was carried out with health-check screening in an area of east-central Japan. We selected 352 individuals whose LDL-C levels were higher than 140 mg/dL from the initially screened 22,228 people. We assessed the relation between plasma cholesterol levels and single-nucleotide polymorphisms (SNPs) in the LRP2 gene. Results: -
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. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Multiple E2 Ubiquitin-Conjugating Enzymes Regulate Human Cytomegalovirus US2-Mediated Immunoreceptor Downregulation Michael L
© 2017. Published by The Company of Biologists Ltd | Journal of Cell Science (2017) 130, 2883-2892 doi:10.1242/jcs.206839 RESEARCH ARTICLE Multiple E2 ubiquitin-conjugating enzymes regulate human cytomegalovirus US2-mediated immunoreceptor downregulation Michael L. van de Weijer1,*,‡, Anouk B. C. Schuren1,‡, Dick J. H. van den Boomen2, Arend Mulder3, Frans H. J. Claas3, Paul J. Lehner2, Robert Jan Lebbink1,§ and Emmanuel J. H. J. Wiertz1,§,¶ ABSTRACT Schuren et al., 2016). At least five unique short (US) regions in the Misfolded endoplasmic reticulum (ER) proteins are dislocated HCMV genome are known to encode proteins that specifically towards the cytosol and degraded by the ubiquitin–proteasome interfere with the expression of HLA-I molecules (van de Weijer system in a process called ER-associated protein degradation et al., 2015). US3 retains newly synthesized HLA-I proteins in the (ERAD). During infection with human cytomegalovirus (HCMV), the ER and blocks tapasin-dependent peptide loading (Jones et al., viral US2 protein targets HLA class I molecules (HLA-I) for 1996; Noriega et al., 2012a; Park et al., 2004). US6 interacts with degradation via ERAD to avoid elimination by the immune system. the transporter associated with antigen processing (TAP) complex US2-mediated degradation of HLA-I serves as a paradigm of ERAD and induces conformational changes of TAP that prevent ATP and has facilitated the identification of TRC8 (also known as RNF139) binding, thereby inhibiting TAP-mediated peptide translocation into as an E3 ubiquitin ligase. No specific E2 enzymes had previously the ER (Ahn et al., 1997; Hengel et al., 1997; Hewitt et al., 2001; been described for cooperation with TRC8. -
Human Megalin/LRP2 Antibody
Human Megalin/LRP2 Antibody Monoclonal Mouse IgG1 Clone # 545606 Catalog Number: MAB9578 DESCRIPTION Species Reactivity Human Specificity Detects human Megalin/LRP2 in direct ELISAs. Source Monoclonal Mouse IgG1 Clone # 545606 Purification Protein A or G purified from ascites Immunogen Mouse myeloma cell line NS0derived recombinant human Megalin/LRP2 Pro3510Lys3964 Accession # P98164 Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. *Small pack size (SP) is supplied either lyophilized or as a 0.2 μm filtered solution in PBS. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Flow Cytometry 0.25 µg/106 cells See Below Immunohistochemistry 525 µg/mL See Below CyTOFready Ready to be labeled using established conjugation methods. No BSA or other carrier proteins that could interfere with conjugation. DATA Flow Cytometry Immunohistochemistry Detection of Megalin/LRP2 in CaCo2 Megalin/LRP2 in Human Kidney. Human Cell Line by Flow Cytometry. Megalin/LRP2 was detected in immersion CaCo2 human cell line was stained with fixed paraffinembedded sections of human Mouse AntiHuman Megalin/LRP2 kidney using Mouse AntiHuman Monoclonal Antibody (Catalog # MAB9578, Megalin/LRP2 Monoclonal Antibody (Catalog filled histogram) or isotype control antibody # MAB9578) at 5 µg/mL for 1 hour at room (Catalog # MAB002, open histogram), temperature followed by incubation with the followed by Phycoerythrinconjugated Anti AntiMouse IgG VisUCyte™ HRP Polymer Mouse IgG Secondary Antibody (Catalog # Antibody (Catalog # VC001). -
Clusterin and LRP2 Are Critical Components of the Hypothalamic Feeding Regulatory Pathway
ARTICLE Received 21 Sep 2012 | Accepted 16 Apr 2013 | Published 14 May 2013 DOI: 10.1038/ncomms2896 Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway So Young Gil1, Byung-Soo Youn2, Kyunghee Byun3,4, Hu Huang5, Churl Namkoong1, Pil-Geum Jang1, Joo-Yong Lee1, Young-Hwan Jo6, Gil Myoung Kang1, Hyun-Kyong Kim1, Mi-Seon Shin7, Claus U. Pietrzik8, Bonghee Lee3,4, Young-Bum Kim3,5 & Min-Seon Kim1,7 Hypothalamic feeding circuits are essential for the maintenance of energy balance. There have been intensive efforts to discover new biological molecules involved in these pathways. Here we report that central administration of clusterin, also called apolipoprotein J, causes anorexia, weight loss and activation of hypothalamic signal transduction-activated transcript-3 in mice. In contrast, inhibition of hypothalamic clusterin action results in increased food intake and body weight, leading to adiposity. These effects are likely mediated through the mutual actions of the low-density lipoprotein receptor-related protein-2, a potential receptor for clusterin, and the long-form leptin receptor. In response to clusterin, the low-density lipoprotein receptor-related protein-2 binding to long-form leptin receptor is greatly enhanced in cultured neuronal cells. Furthermore, long-form leptin receptor deficiency or hypothalamic low-density lipoprotein receptor-related protein-2 suppression in mice leads to impaired hypothalamic clusterin signalling and actions. Our study identifies the hypotha- lamic clusterin–low-density lipoprotein receptor-related protein-2 axis as a novel anorexigenic signalling pathway that is tightly coupled with long-form leptin receptor-mediated signalling. 1 Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul 138-736, Korea. -
Characterization of the Cellular Network of Ubiquitin Conjugating and Ligating Enzymes Ewa Katarzyna Blaszczak
Characterization of the cellular network of ubiquitin conjugating and ligating enzymes Ewa Katarzyna Blaszczak To cite this version: Ewa Katarzyna Blaszczak. Characterization of the cellular network of ubiquitin conjugating and ligating enzymes. Cellular Biology. Université Rennes 1, 2015. English. NNT : 2015REN1S116. tel-01547616 HAL Id: tel-01547616 https://tel.archives-ouvertes.fr/tel-01547616 Submitted on 27 Jun 2017 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. ANNÉE 2015 THÈSE / UNIVERSITÉ DE RENNES 1 sous le sceau de l’Université Européenne de Bretagne pour le grade de DOCTEUR DE L’UNIVERSITÉ DE RENNES 1 Mention : BIOLOGIE École doctorale Vie-Agro-Santé présentée par Ewa Katarzyna Blaszczak Préparée à l’unité de recherche UMR 6290, IGDR Institut de Génétique et Développement de Rennes Université Rennes 1 Thèse soutenue à Rennes le 26.06.2015 Characterization of devant le jury composé de : Aude ECHALIER-GLAZER the cellular network Maître de conférence University of Leicester / rapporteur of ubiquitin Lionel PINTARD Directeur de recherche -
Plasma Proteomic Analysis Reveals Altered Protein Abundances In
Lygirou et al. J Transl Med (2018) 16:104 https://doi.org/10.1186/s12967-018-1476-9 Journal of Translational Medicine RESEARCH Open Access Plasma proteomic analysis reveals altered protein abundances in cardiovascular disease Vasiliki Lygirou1 , Agnieszka Latosinska2, Manousos Makridakis1, William Mullen3, Christian Delles3, Joost P. Schanstra4,5, Jerome Zoidakis1, Burkert Pieske6, Harald Mischak2 and Antonia Vlahou1* Abstract Background: Cardiovascular disease (CVD) describes the pathological conditions of the heart and blood vessels. Despite the large number of studies on CVD and its etiology, its key modulators remain largely unknown. To this end, we performed a comprehensive proteomic analysis of blood plasma, with the scope to identify disease-associated changes after placing them in the context of existing knowledge, and generate a well characterized dataset for fur- ther use in CVD multi-omics integrative analysis. Methods: LC–MS/MS was employed to analyze plasma from 32 subjects (19 cases of various CVD phenotypes and 13 controls) in two steps: discovery (13 cases and 8 controls) and test (6 cases and 5 controls) set analysis. Follow- ing label-free quantifcation, the detected proteins were correlated to existing plasma proteomics datasets (plasma proteome database; PPD) and functionally annotated (Cytoscape, Ingenuity Pathway Analysis). Diferential expression was defned based on identifcation confdence ( 2 peptides per protein), statistical signifcance (Mann–Whitney p value 0.05) and a minimum of twofold change.≥ ≤ Results: Peptides detected in at least 50% of samples per group were considered, resulting in a total of 3796 identi- fed proteins (838 proteins based on 2 peptides). Pathway annotation confrmed the functional relevance of the fndings (representation of complement≥ cascade, fbrin clot formation, platelet degranulation, etc.). -
Ubiquitylation of P62/Sequestosome1 Activates Its Autophagy Receptor Function and Controls Selective Autophagy Upon Ubiquitin Stress
Cell Research (2017) 27:657-674. © 2017 IBCB, SIBS, CAS All rights reserved 1001-0602/17 $ 32.00 ORIGINAL ARTICLE www.nature.com/cr Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress Hong Peng1, 2, 3, *, Jiao Yang1, 2, 3, *, Guangyi Li1, 2, Qing You1, 2, Wen Han1, Tianrang Li1, Daming Gao1, Xiaoduo Xie1, Byung-Hoon Lee4, Juan Du5, Jian Hou5, Tao Zhang6, Hai Rao7, Ying Huang3, Qinrun Li1, Rong Zeng1, Lijian Hui3, Hongyan Wang1, Qin Xia8, Xuemin Zhang8, Yongning He3, Masaaki Komatsu9, Ivan Dikic10, Daniel Finley4, Ronggui Hu1 1Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, 2Graduate School, University of Chinese Academy of Sciences; 3Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; 4Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA; 5Department of Hematology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China; 6Department of Laboratory Medicine, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China; 7Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA; 8State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China; 9Department of Biochemistry, School of Medicine Niigata University, 757, Ichibancho, Asahimachidori, Chuo-ku, Niigata 951-8510, Japan; 10Molecular Signaling, Institute of Biochemistry II, Goethe University School of Medicine, 60590 Frankfurt am Main, Germany Alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. -
A New Role for LRP2 in Forebrain Development
A new role for LRP2 in forebrain development DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) im Fach Biologie eingereicht an der Mathematisch-Naturwissenschaftlichen Fakult¨atI Humboldt-Universit¨atzu Berlin von Herr Dipl.-Biol. (technisch orientiert) Uwe Anzenberger geboren am 22.03.1976 in Singen a. Htwl. Pr¨asident der Humboldt-Universit¨atzu Berlin: Prof. Dr. Christoph Markschies Dekan der Mathematisch-Naturwissenschaftlichen Fakult¨atI: Prof. Thomas Buckhout, Phd Gutachter: 1. Prof. Dr. Thomas Willnow 2. Prof. Dr. Michael Bader 3. Prof. Dr. Wolfgang Lockau Tag der m¨undlichen Pr¨ufung: 22. September 2006 Abstract LRP2 is a member of the low-density lipoprotein receptor gene family that is mainly expressed in the yolk sac and in the neuroepithelium of the early embryo. Deficiency for this 600 kDa protein in mice results in holoprosencephaly, indicating an important yet unknown role for LRP2 in forebrain development. In this study, mice with a complete or a conditional loss of lrp2 function were used to further elucidate the consequences of the lack of LRP2 expression. This study shows that the presence of LRP2 in the neuroepithelium but not in the yolk sac is crucial for early forebrain development. Lack of the receptor resulted in an increase of Bone morphogenic protein (Bmp) 4 signaling in the rostral telencephalon at E9.5. As a consequence, sonic hedgehog (shh) expression at E10.5 was lost completely in a ventral region of the telencephalon termed anterior entopeduncular area (AEP). The absence of Shh activity in this area subsequently led to the loss of ventrally induced oligodendroglial and interneuronal cell populations in lrp2 deficient mice.