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Lupus-Associated Endogenous Retroviral LTR Polymorphism and Epigenetic Imprinting Promote HRES-1/Rab4 Expression and Mtor Activation
Lupus-associated endogenous retroviral LTR polymorphism and epigenetic imprinting promote HRES-1/Rab4 expression and mTOR activation Aparna Godavarthy, … , Katalin Banki, Andras Perl JCI Insight. 2019. https://doi.org/10.1172/jci.insight.134010. Research In-Press Preview Immunology Graphical abstract Find the latest version: https://jci.me/134010/pdf LUPUS-ASSOCIATED ENDOGENOUS RETROVIRAL LTR POLYMORPHISM AND EPIGENETIC IMPRINTING PROMOTE HRES-1/RAB4 EXPRESSION AND MTOR ACTIVATION Aparna Godavarthy*1, Ryan Kelly*1, John Jimah1, Miguel Beckford1, Tiffany Caza1,2, David Fernandez1,2, Nick Huang1,3, Manuel Duarte1,2, Joshua Lewis1,2, Hind J. Fadel4, Eric M. Poeschla4, Katalin Banki5, and Andras Perl1,2,3 * These authors contributed equally to the study. 1, Division of Rheumatology, Department of Medicine; 2, Department of Microbiology and Immunology; 3, Department of Biochemistry and Molecular Biology, and 5, Department of Pathology, State University of New York, Upstate Medical University, College of Medicine, 750 East Adams Street, Syracuse, New York 13210; 4, Department of Molecular Medicine; Mayo Clinic College of Medicine, 200 First Street SW, Rochester 55905, USA; Correspondence: Andras Perl, M.D., Ph.D. , State University of New York, College of Medicine, 750 East Adams Street, Syracuse, New York 13210; Phone: (315) 464-4194; Fax: (315) 464- 4176; E-mail: [email protected] Key Words: Systemic Lupus Erythematosus, T Cells, HRES-1/Rab4. mTOR, Autoimmunity The authors have declared that no conflict of interest exists. Supplementary Materials include Supplemental Methods and Supplementary Figures S1-S26. 1 ABSTRACT Overexpression and long terminal repeat (LTR) polymorphism of the HRES-1/Rab4 human endogenous retrovirus locus have been associated with T-cell activation and disease manifestations in systemic lupus erythematosus (SLE). -
Transportin 1 Accumulates Specifically with FET Proteins but No Other
CORE Metadata, citation and similar papers at core.ac.uk Provided by RERO DOC Digital Library Acta Neuropathol DOI 10.1007/s00401-012-1020-6 ORIGINAL PAPER Transportin 1 accumulates specifically with FET proteins but no other transportin cargos in FTLD-FUS and is absent in FUS inclusions in ALS with FUS mutations Manuela Neumann • Chiara F. Valori • Olaf Ansorge • Hans A. Kretzschmar • David G. Munoz • Hirofumi Kusaka • Osamu Yokota • Kenji Ishihara • Lee-Cyn Ang • Juan M. Bilbao • Ian R. A. Mackenzie Received: 22 May 2012 / Accepted: 16 July 2012 Ó Springer-Verlag 2012 Abstract Accumulation of the DNA/RNA binding pro- in these conditions. While ALS-FUS showed only accu- tein fused in sarcoma (FUS) as inclusions in neurons and mulation of FUS, inclusions in FTLD-FUS revealed co- glia is the pathological hallmark of amyotrophic lateral accumulation of all members of the FET protein family, that sclerosis patients with mutations in FUS (ALS-FUS) as well include FUS, Ewing’s sarcoma (EWS) and TATA-binding as in several subtypes of frontotemporal lobar degeneration protein-associated factor 15 (TAF15) suggesting a more (FTLD-FUS), which are not associated with FUS muta- complex disturbance of transportin-mediated nuclear tions. Despite some overlap in the phenotype and import of proteins in FTLD-FUS compared to ALS-FUS. neuropathology of FTLD-FUS and ALS-FUS, significant To gain more insight into the mechanisms of inclusion body differences of potential pathomechanistic relevance were formation, we investigated the role of Transportin 1 (Trn1) recently identified in the protein composition of inclusions as well as 13 additional cargo proteins of Transportin in the spectrum of FUS-opathies by immunohistochemistry and biochemically. -
FUS-NLS/Transportin 1 Complex Structure Provides
University of Kentucky UKnowledge Molecular and Cellular Biochemistry Faculty Molecular and Cellular Biochemistry Publications 10-8-2012 FUS-NLS/Transportin 1 complex structure provides insights into the nuclear targeting mechanism of FUS and the implications in ALS Chunyan Niu Chinese Academy of Sciences, China Jiayu Zhang University of Kentucky, [email protected] Feng Gao Chinese Academy of Sciences, China Liuqing Yang University of Kentucky, [email protected] Minze Jia Chinese Academy of Sciences, China See next page for additional authors Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/biochem_facpub Part of the Biochemistry, Biophysics, and Structural Biology Commons Repository Citation Niu, Chunyan; Zhang, Jiayu; Gao, Feng; Yang, Liuqing; Jia, Minze; Zhu, Haining; and Gong, Weimin, "FUS-NLS/Transportin 1 complex structure provides insights into the nuclear targeting mechanism of FUS and the implications in ALS" (2012). Molecular and Cellular Biochemistry Faculty Publications. 9. https://uknowledge.uky.edu/biochem_facpub/9 This Article is brought to you for free and open access by the Molecular and Cellular Biochemistry at UKnowledge. It has been accepted for inclusion in Molecular and Cellular Biochemistry Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Authors Chunyan Niu, Jiayu Zhang, Feng Gao, Liuqing Yang, Minze Jia, Haining Zhu, and Weimin Gong FUS-NLS/Transportin 1 complex structure provides insights into the nuclear targeting mechanism of FUS and the implications in ALS Notes/Citation Information Published in PLoS ONE, v. -
Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS
Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen, -
A Universal Transportin Protein Drives Stochastic Choice of Olfactory Neurons Via Specific Nuclear Import of a Sox-2-Activating Factor
A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor Amel Alqadaha, Yi-Wen Hsieha,1, Rui Xionga,1, Bluma J. Leschb, Chieh Changa, and Chiou-Fen Chuanga,2 aDepartment of Biological Sciences, University of Illinois at Chicago, IL 60607; and bDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510 Edited by Iva Greenwald, Columbia University, New York, NY, and approved October 31, 2019 (received for review June 25, 2019) Stochastic neuronal cell fate choice involving notch-independent mechanisms act downstream of the BK potassium channels to mechanisms is a poorly understood biological process. The induce the AWCON identity. Caenorhabditis elegans AWC olfactory neuron pair asymmetrically Here, we identify a role of the karyopherin imb-2/transportin 1 differentiates into the default AWCOFF and induced AWCON subtypes downstream of the SLO BK potassium channels in promoting in a stochastic manner. Stochastic choice of the AWCON subtype is the AWCON subtype from an unbiased forward genetic screen. established using gap junctions and SLO BK potassium channels to We show that asymmetrical expression of imb-2 in AWCON cells, repress a calcium-activated protein kinase pathway. However, it is which is dependent on nsy-5 (gap junction) and slo-1 (BK po- unknown how the potassium channel-repressed calcium signaling is tassium channel), is necessary and sufficient for AWC asymmetry. translated into the induction of the AWCON subtype. Here, we iden- In addition, IMB-2 localizes in close proximity to the homeo- tify a detailed working mechanism of how the homeodomain-like domain-like transcription factor NSY-7 and mediates nuclear transcription factor NSY-7, previously described as a repressor in the transport of NSY-7 to specify the AWCON subtype. -
Protein Nuclear Import and Beyond ⇑ Laure Twyffels A,B, , Cyril Gueydan A,1, Véronique Kruys A,B,1
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 588 (2014) 1857–1868 journal homepage: www.FEBSLetters.org Review Transportin-1 and Transportin-2: Protein nuclear import and beyond ⇑ Laure Twyffels a,b, , Cyril Gueydan a,1, Véronique Kruys a,b,1 a Laboratoire de Biologie moléculaire du gène (CP300), Faculté des Sciences, Université Libre de Bruxelles (ULB), Belgium b Center for Microscopy and Molecular Imaging (CMMI), 6041 Gosselies, Belgium article info abstract Article history: Nearly 20 years after its identification as a new b-karyopherin mediating the nuclear import of the Received 15 February 2014 RNA-binding protein hnRNP A1, Transportin-1 is still commonly overlooked in comparison with its Revised 12 April 2014 best known cousin, Importin-b. Transportin-1 is nonetheless a considerable player in nucleo-cyto- Accepted 16 April 2014 plasmic transport. Over the past few years, significant progress has been made in the characteriza- Available online 26 April 2014 tion of the nuclear localization signals (NLSs) that Transportin-1 recognizes, thereby providing the Edited by Ulrike Kutay molecular basis of its diversified repertoire of cargoes. The recent discovery that mutations in the Transportin-dependent NLS of FUS cause mislocalization of this protein and result in amyotrophic lateral sclerosis illustrates the importance of Transportin-dependent import for human health. Keywords: Transportin Besides, new functions of Transportin-1 are emerging in processes other than nuclear import. Here, Importins we summarize what is known about Transportin-1 and the related b-karyopherin Transportin-2. Karyopherins Ó 2014 Federation of European Biochemical Societies. -
Molecular Effects of Isoflavone Supplementation Human Intervention Studies and Quantitative Models for Risk Assessment
Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis committee Promotors Prof. Dr Pieter van ‘t Veer Professor of Nutritional Epidemiology Wageningen University Prof. Dr Evert G. Schouten Emeritus Professor of Epidemiology and Prevention Wageningen University Co-promotors Dr Anouk Geelen Assistant professor, Division of Human Nutrition Wageningen University Dr Lydia A. Afman Assistant professor, Division of Human Nutrition Wageningen University Other members Prof. Dr Jaap Keijer, Wageningen University Dr Hubert P.J.M. Noteborn, Netherlands Food en Consumer Product Safety Authority Prof. Dr Yvonne T. van der Schouw, UMC Utrecht Dr Wendy L. Hall, King’s College London This research was conducted under the auspices of the Graduate School VLAG (Advanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. Dr M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Friday 20 June 2014 at 13.30 p.m. in the Aula. Vera van der Velpen Molecular effects of isoflavone supplementation: Human intervention studies and quantitative models for risk assessment 154 pages PhD thesis, Wageningen University, Wageningen, NL (2014) With references, with summaries in Dutch and English ISBN: 978-94-6173-952-0 ABSTRact Background: Risk assessment can potentially be improved by closely linked experiments in the disciplines of epidemiology and toxicology. -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Distinct Splicing Signatures Affect Converged Pathways in Myelodysplastic Syndrome Patients Carrying Mutations in Different Splicing Regulators
Downloaded from rnajournal.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators JINSONG QIU,1,7 BING ZHOU,1,7 FELICITAS THOL,2 YU ZHOU,1 LIANG CHEN,1 CHANGWEI SHAO,1 CHRISTOPHER DEBOEVER,3 JIAYI HOU,4 HAIRI LI,1 ANUHAR CHATURVEDI,2 ARNOLD GANSER,2 RAFAEL BEJAR,5 DONG-ER ZHANG,6 XIANG-DONG FU,1,3 and MICHAEL HEUSER2 1Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA 2Department of Hematology, Hemostasis, Oncology and Stem cell Transplantation, Hannover Medical School, 30625 Hannover, Germany 3Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA 4Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California 92093, USA 5Division of Hematology-Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA 6Department of Pathology, Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA ABSTRACT Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders with prevalent mutations in several splicing factors, but the splicing programs linked to specific mutations or MDS in general remain to be systematically defined. We applied RASL-seq, a sensitive and cost-effective platform, to interrogate 5502 annotated splicing events in 169 samples from MDS patients or healthy individuals. We found that splicing signatures associated with normal hematopoietic lineages are largely related to cell signaling and differentiation programs, whereas MDS-linked signatures are primarily involved in cell cycle control and DNA damage responses. -
Role and Regulation of the P53-Homolog P73 in the Transformation of Normal Human Fibroblasts
Role and regulation of the p53-homolog p73 in the transformation of normal human fibroblasts Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayerischen Julius-Maximilians-Universität Würzburg vorgelegt von Lars Hofmann aus Aschaffenburg Würzburg 2007 Eingereicht am Mitglieder der Promotionskommission: Vorsitzender: Prof. Dr. Dr. Martin J. Müller Gutachter: Prof. Dr. Michael P. Schön Gutachter : Prof. Dr. Georg Krohne Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am Erklärung Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig angefertigt und keine anderen als die angegebenen Hilfsmittel und Quellen verwendet habe. Diese Arbeit wurde weder in gleicher noch in ähnlicher Form in einem anderen Prüfungsverfahren vorgelegt. Ich habe früher, außer den mit dem Zulassungsgesuch urkundlichen Graden, keine weiteren akademischen Grade erworben und zu erwerben gesucht. Würzburg, Lars Hofmann Content SUMMARY ................................................................................................................ IV ZUSAMMENFASSUNG ............................................................................................. V 1. INTRODUCTION ................................................................................................. 1 1.1. Molecular basics of cancer .......................................................................................... 1 1.2. Early research on tumorigenesis ................................................................................. 3 1.3. Developing -
Open Data for Differential Network Analysis in Glioma
International Journal of Molecular Sciences Article Open Data for Differential Network Analysis in Glioma , Claire Jean-Quartier * y , Fleur Jeanquartier y and Andreas Holzinger Holzinger Group HCI-KDD, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 2/V, 8036 Graz, Austria; [email protected] (F.J.); [email protected] (A.H.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 27 October 2019; Accepted: 3 January 2020; Published: 15 January 2020 Abstract: The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes. -
Retroviral Vector Integration Deregulates Gene Expression but Has No Consequence on the Biology and Function of Transplanted T Cells
Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells Alessandra Recchia*†, Chiara Bonini*‡, Zulma Magnani*, Fabrizia Urbinati†, Daniela Sartori*§, Sara Muraro*, Enrico Tagliafico†, Attilio Bondanza*¶, Maria Teresa Lupo Stanghellini‡, Massimo Bernardi‡, Alessandra Pescarollo‡, Fabio Ciceri‡, Claudio Bordignon§¶, and Fulvio Mavilio†ʈ *Cancer Immunotherapy and Gene Therapy Program, and ‡Bone Marrow Transplantation Unit, Istituto Scientifico H. San Raffaele, Via Olgettina 58, 20132 Milan, Italy; †Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy; §MolMed S.p.A., Via Olgettina 58, 20132 Milan, Italy; and ¶San Raffaele ‘‘Vita e Salute’’ University, Via Olgettina 58, 20132 Milan, Italy Edited by Malcolm A. Martin, National Institutes of Health, Bethesda, MD, and approved December 6, 2005 (received for review September 1, 2005) The use of retroviral vectors in gene therapy has raised safety is currently profiled to provide a graft-versus-leukemia effect to concerns for the genotoxic risk associated with their uncontrolled patients in relapse after HLA-identical HSC transplantation (14), insertion into the human genome. We have analyzed the conse- or to promote immune reconstitution and prevent relapse in quences of retroviral transduction in T cells from leukemic patients patients undergoing HLA-haploidentical HSC transplantation. In treated with allogeneic stem cell transplantation and donor lym- 46 patients treated since 1994 in both contexts, we were able to phocytes genetically modified with a suicide gene (HSV-TK). Ret- control GvHD in 100% of the cases, while preserving antiviral and roviral vectors integrate preferentially within or near transcribed antitumor activity (14–16).