A Trans Locus Causes a Ribosomopathy in Hypertrophic Hearts That Affects
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The Inhibition of LSD1 Via Sequestration Contributes to Tau-Mediated Neurodegeneration
The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration Amanda K. Engstroma, Alicia C. Walkera, Rohitha A. Moudgala, Dexter A. Myricka, Stephanie M. Kylea, Yu Baia, M. Jordan Rowleyb, and David J. Katza,1 aDepartment of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322; and bDepartment of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198 Edited by Michele Pagano, HHMI and New York University School of Medicine, New York, NY, and accepted by Editorial Board Member Gail Mandel October 1, 2020 (received for review July 2, 2020) Tauopathies are a class of neurodegenerative diseases associated AD cases, but not other neurodegenerative diseases, such as with pathological tau. Despite many advances in our understand- Parkinson’s disease or amyotrophic lateral sclerosis (ALS) cases. ing of these diseases, the direct mechanism through which tau Consistent with this overlap, we observed LSD1 protein mis- contributes to neurodegeneration remains poorly understood. Pre- localized to cytoplasmic NFTs, but not associated with Aβ plaques viously, our laboratory implicated the histone demethylase LSD1 in in AD cases or Lewy bodies of α-synuclein in Parkinson’sdisease tau-induced neurodegeneration by showing that LSD1 localizes to cases (26). In control cases, LSD1 remains strictly confined to the pathological tau aggregates in Alzheimer’s disease cases, and that it nucleus (26), due to its well-defined nuclear localization signal is continuously required for the survival of hippocampal and cortical (27). These data highlight the requirement for LSD1 in neuro- neurons in mice. Here, we utilize the P301S tauopathy mouse model nal survival and suggest that the nuclear function of the histone to demonstrate that pathological tau can exclude LSD1 from the demethylase LSD1 could be disrupted by mislocalization to nucleus in neurons. -
Dual Proteome-Scale Networks Reveal Cell-Specific Remodeling of the Human Interactome
bioRxiv preprint doi: https://doi.org/10.1101/2020.01.19.905109; this version posted January 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome Edward L. Huttlin1*, Raphael J. Bruckner1,3, Jose Navarrete-Perea1, Joe R. Cannon1,4, Kurt Baltier1,5, Fana Gebreab1, Melanie P. Gygi1, Alexandra Thornock1, Gabriela Zarraga1,6, Stanley Tam1,7, John Szpyt1, Alexandra Panov1, Hannah Parzen1,8, Sipei Fu1, Arvene Golbazi1, Eila Maenpaa1, Keegan Stricker1, Sanjukta Guha Thakurta1, Ramin Rad1, Joshua Pan2, David P. Nusinow1, Joao A. Paulo1, Devin K. Schweppe1, Laura Pontano Vaites1, J. Wade Harper1*, Steven P. Gygi1*# 1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA. 2Broad Institute, Cambridge, MA, 02142, USA. 3Present address: ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, 02115, USA. 4Present address: Merck, West Point, PA, 19486, USA. 5Present address: IQ Proteomics, Cambridge, MA, 02139, USA. 6Present address: Vor Biopharma, Cambridge, MA, 02142, USA. 7Present address: Rubius Therapeutics, Cambridge, MA, 02139, USA. 8Present address: RPS North America, South Kingstown, RI, 02879, USA. *Correspondence: [email protected] (E.L.H.), [email protected] (J.W.H.), [email protected] (S.P.G.) #Lead Contact: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.01.19.905109; this version posted January 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
ENDOG Impacts on Tumor Cell Proliferation and Tumor Prognosis in the Context of PI3K/PTEN Pathway Status
cancers Article ENDOG Impacts on Tumor Cell Proliferation and Tumor Prognosis in the Context of PI3K/PTEN Pathway Status Gisel Barés 1,†, Aida Beà 1,†, Luís Hernández 2,* , Raul Navaridas 3, Isidre Felip 3, Cristina Megino 3 , Natividad Blasco 1,‡, Ferran Nadeu 2 , Elías Campo 2,4, Marta Llovera 1 , Xavier Dolcet 3 and Daniel Sanchis 1,* 1 Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida-IRBLleida, 25198 Lleida, Spain; [email protected] (G.B.); [email protected] (A.B.); [email protected] (N.B.); [email protected] (M.L.) 2 Lymphoid Neoplasm Program, Institut d’Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS) and CIBERONC, 08036 Barcelona, Spain; [email protected] (F.N.); [email protected] (E.C.) 3 Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida–IRBLleida and CIBERONC, 25198 Lleida, Spain; [email protected] (R.N.); [email protected] (I.F.); [email protected] (C.M.); [email protected] (X.D.) 4 Department of Oncology, Hospital Clinic of Barcelona, Universitat de Barcelona, 08036 Barcelona, Spain * Correspondence: [email protected] (L.H.); [email protected] (D.S.); Tel.: +34-(97)-375-2949 (D.S.) † These authors contributed equally to this work (co-first authors). ‡ Present address: Grupo LMA Fundación PETHEMA, Laboratorio de Biología Molecular, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain. Simple Summary: The PI3K/AKT pathway is involved in cell survival and proliferation. Molecular aberrations and/or hyperactivation of the PI3K-PTEN-AKT axis are frequent in distinct cancer types such as endometrial carcinoma, the most common type of cancer of the female genital tract, and chronic lymphocytic leukemia (CLL), a mature B-cell neoplasm depending on B-cell receptor (BCR) activity, which induces chronical activation of this pathway. -
High-Density Single Nucleotide Polymorphism Array Defines Novel Stage and Location-Dependent Allelic Imbalances in Human Bladder Tumors
ResearchResearch Article Article High-Density Single Nucleotide Polymorphism Array Defines Novel Stage and Location-Dependent Allelic Imbalances in Human Bladder Tumors Karen Koed,1,3 Carsten Wiuf,4 Lise-Lotte Christensen,1 Friedrik P. Wikman,1 Karsten Zieger,1,2 Klaus Møller,2 Hans von der Maase,3 and Torben F. Ørntoft1 Molecular Diagnostic Laboratory, 1Departments of Clinical Biochemistry, 2Urology, and 3Oncology, Aarhus University Hospital; and 4Bioinformatics Research Center, Aarhus University, Aarhus, Denmark Abstract In the case of noninvasive Ta transitional cell carcinomas, this Bladder cancer is a common disease characterized by multiple includes loss of chromosome 9, or parts of it, as well as 1q+ and loss recurrences and an invasive disease course in more than 10% of the Y chromosome in males (2, 5). In invasive tumors, many of patients. It is of monoclonal or oligoclonal origin and alterations have been reported to be more or less common: 1pÀ, genomic instability has been shown at certain loci. We used a 2qÀ,4qÀ,5qÀ,8pÀ, À9, 10qÀ, 11pÀ,11qÀ, 1q+, 2p+, 5p+, 8q+, 10,000 single nucleotide polymorphism (SNP) array with an 11q13+, 17q+, and 20q+ (2, 6–8). It has been suggested that these lost average of 2,700 heterozygous SNPs to detect allelic imbalances or gained regions harbor tumor suppressor genes and oncogenes, (AI) in 37 microdissected bladder tumors from 17 patients. respectively. However, the large chromosomal areas involved often Eight tumors represented upstaging from Ta to T1, eight from contain many genes, making meaningful predictions of the T1 to T2+, and one from Ta to T2+. -
Is Swachman-Diamond Syndrome a Ribosomopathy?
Downloaded from genesdev.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press PERSPECTIVE Of blood, bones, and ribosomes: is Swachman-Diamond syndrome a ribosomopathy? Arlen W. Johnson1,3 and Steve R. Ellis2 1Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin Texas 78712, USA; 2Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA Mutations in the human SBDS (Shwachman-Bodian-Di- regulation (Ambekar et al. 2010), and stabilizing the amond syndrome) gene are the most common cause of mitotic spindle (Austin et al. 2008). This has led to the Shwachman-Diamond syndrome, an inherited bone mar- suggestion that SBDS is a multifunctional protein, which row failure syndrome. In this issue of Genes & Develop- in turn has led to considerable discussion about which, ment, Finch and colleagues (pp. 917–929) establish that if any, clinical features of SDS are due to defects in SBDS functions in ribosome synthesis by promoting the ribosome production, and which can be attributed to recycling of eukaryotic initiation factor 6 (eIF6) in a GTP- a role for SBDS in other cellular pathways. The study by dependent manner. This work supports the idea that Finch et al. (2011) in this issue of Genes & Development a ribosomopathy may underlie this syndrome. clearly defines a role of SBDS in ribosome synthesis in mammalian cells. This knowledge represents an impor- tant step in ongoing efforts to equate clinical features of SDS with cellular processes affected by loss-of-function Shwachman-Diamond syndrome (SDS) is an inherited mutations in SBDS. -
Association of Endonuclease G Gene Variants with Cardiovascular Disease Risk Factors
Reports of Biochemistry & Molecular Biology Vol.8, No.2, July 2019 Original article www.RBMB.net Association of Endonuclease G Gene Variants with Cardiovascular Disease Risk Factors Negar Etehad Roodi#1, Nushin Karkuki Osguei#2, Mahdy Hasanzadeh Daloee3, Alireza Pasdar4, Majid Ghayour-Mobarhan5, Gordon Ferns6, Ali Samadi Kuchaksaraei*¹ Abstract Background: Cardiovascular disease (CVD) is a leading cause of death, supporting the need for the identification of novel biomarkers as risk stratification factors. Endonuclease G (ENDOG) has recently been suggested to be a novel determinant of cardiac hypertrophy and mitochondrial function, and plays an important role in apoptosis processes involved in cardiac myocyte death. The aim of current study was to explore the association of two genetic variants in ENDOG gene (ENDOG) with CVD risk factors in an Iranian population. Methods: Subjects included 663 patients with CVD and 282 healthy individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders Cohort Study. The ENDOG S12L (rs 2293969) and L142M (rs 61397314) variants were genotyped. Anthropometric and biochemical factors were measured in all the subjects followed by univariate and multivariate analyses to determine the association of these genetic markers with CVD and biochemical parameters. Results: ENDOG polymorphisms were found at a significantly higher prevalence in individuals who had histories of smoking and breaking point in L142M. In contrast, other risk factors for cardiovascular disease, including lipid profile and blood pressure, showed no or very weak relationship with the ENDOG polymorphisms. Conclusions: Our findings indicated an association between an ENDOG genetic variant and smoking history as a cardiovascular risk factor. Further studies in the prospective setting are warranted to investigate the value of this marker. -
Role of Endog in Development and Cell Injury
Letters to the Editor 1971 very low in pre-treatment samples and it is strongly increased S Mainardi1, A Pelosi1, E Palescandolo2, R Riccioni3, in 18 out of 22 patients (81.8%) after therapy (Supplementary G Fontemaggi1,4, D Diverio5, U Testa3, A Sacchi1, Figure 3). F Grignani6, F Lo-Coco7, M Levrero2,4,8, G Blandino*,1,4 Altogether, our findings show that DN-p73 is a transcrip- and MG Rizzo*,1 tional target of the PML/RARa oncogene. This results in the transcriptional repression of DN-p73 providing one potential 1 Department of Experimental Oncology, Laboratory of Molecular Oncogenesis, molecular basis underlying the lack of DN-p73 expression in a Regina Elena Cancer Institute, Rome, Italy; large subset of APL leukemias. The role of PML/RARa in 2 Department of Internal Medicine, Laboratory of Gene Expression, Fondazione DN-p73 repression is confirmed by the ability of RA to restore Andrea Cesalpino, University of Rome ‘La Sapienza’, Rome, Italy; 3 its expression both in vitro and in vivo. The observation that Laboratory of Hematology and Oncology, Istituto Superiore di Sanita`, Rome, DN-p73 expression induces a number of differentiation Italy; 4 Rome Oncogenomic Center (ROC), Rome, Italy; markers in APL cells and cooperates with RA-induced 5 Department of Cellular Biotechnologies and Hematology, University of Rome differentiation in vitro suggests that DN-p73 might be ‘La Sapienza’, Rome, Italy; necessary for proper myeloid differentiation. Indeed, DN-p73 6 Department of Medicina Clinica e Sperimentale, Medicina Interna e Scienze expression -
Temporal Proteomic Analysis of HIV Infection Reveals Remodelling of The
1 1 Temporal proteomic analysis of HIV infection reveals 2 remodelling of the host phosphoproteome 3 by lentiviral Vif variants 4 5 Edward JD Greenwood 1,2,*, Nicholas J Matheson1,2,*, Kim Wals1, Dick JH van den Boomen1, 6 Robin Antrobus1, James C Williamson1, Paul J Lehner1,* 7 1. Cambridge Institute for Medical Research, Department of Medicine, University of 8 Cambridge, Cambridge, CB2 0XY, UK. 9 2. These authors contributed equally to this work. 10 *Correspondence: [email protected]; [email protected]; [email protected] 11 12 Abstract 13 Viruses manipulate host factors to enhance their replication and evade cellular restriction. 14 We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a 15 comprehensive time course analysis of >6,500 viral and cellular proteins during HIV 16 infection. To enable specific functional predictions, we categorized cellular proteins regulated 17 by HIV according to their patterns of temporal expression. We focussed on proteins depleted 18 with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be 19 necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the 20 B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). 21 Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent 22 hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. 23 The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral 2 24 lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and 25 conserved Vif function. -
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 -
Clinical Impact of Copy Number Variation Changes in Bladder Cancer Samples
EXPERIMENTAL AND THERAPEUTIC MEDICINE 22: 901, 2021 Clinical impact of copy number variation changes in bladder cancer samples VICTORIA SPASOVA1, BORIS MLADENOV2, SIMEON RANGELOV3, ZORA HAMMOUDEH1, DESISLAVA NESHEVA1, DIMITAR SERBEZOV1, RADA STANEVA1,4, SAVINA HADJIDEKOVA1,4, MIHAIL GANEV1, LUBOMIR BALABANSKI1,5, RADOSLAVA VAZHAROVA5,6, CHAVDAR SLAVOV3, DRAGA TONCHEVA1 and OLGA ANTONOVA1 1Department of Medical Genetics, Medical University‑Sofia, 1431 Sofia;2 Department of Urology, UMBALSM N.I. Pirogov, 1606 Sofia; 3Department of Urology, Tsaritsa Yoanna University Hospital, 1527 Sofia; 4Medical Genetics Laboratory, Nadezhda Women's Health Hospital, 1373 Sofia; 5Medical Genetics Laboratory, GARH Malinov, 1680 Sofia; 6Department of Biology, Medical Genetics and Microbiology, Faculty of Medicine, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria Received November 30, 2019; Accepted February 18, 2021 DOI: 10.3892/etm.2021.10333 Abstract. The aim of the present study was to detect copy uroepithelial tumours may lay a foundation for implementing number variations (CNVs) related to tumour progression and molecular CNV profiling of bladder tumours as part of a metastasis of urothelial carcinoma through whole‑genome routine progression risk estimation strategy, thus expanding scanning. A total of 30 bladder cancer samples staged from the personalized therapeutic approach. pTa to pT4 were included in the study. DNA was extracted from freshly frozen tissue via standard phenol‑chloroform extraction Introduction and CNV analysis was performed on two alternative platforms (CytoChip Oligo aCGH, 4x44K and Infinium OncoArray‑500K The most successful approach to treating a disease has BeadChip; Illumina, Inc.). Data were analysed with BlueFuse always been etiological therapy. In the case of bladder Multi software and Karyostudio, respectively. -
DKC1 Is a Transcriptional Target of GATA1 and Drives Upregulation of Telomerase Activity Ferrata Storti Foundation in Normal Human Erythroblasts
Hematopoiesis ARTICLE DKC1 is a transcriptional target of GATA1 and drives upregulation of telomerase activity Ferrata Storti Foundation in normal human erythroblasts Laura A. Richards,1* Ashu Kumari,1* Kathy Knezevic,2 Julie AI Thoms,2,3 Georg von Jonquieres,1 Christine E. Napier,1 Zara Ali,4 Rosemary O’Brien,1 Jonathon Marks-Bluth,2 Michelle F. Maritz,1 Hilda A Pickett,5 Jonathan Morris,6 John E. Pimanda2,3 and Karen L. MacKenzie1,4,7,8 1Children’s Cancer Institute Australia, Randwick; 2Adult Cancer Program, Prince of Wales 3 Haematologica 2020 Clinical School, Lowy Cancer Research Centre, UNSW, Sydney; School of Medical Sciences, UNSW, Sydney; 4Cancer Research Unit, Children’s Medical Research Institute, Volume 105(6):1517-1526 Westmead; 5Telomere Length Regulation Unit, Children’s Medical Research Institute, Westmead; 6The University of Sydney School of Medicine, Kolling Institute of Medical Research, St Leonards; 7School of Women’s and Children’s Health, UNSW, Sydney and 8Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia *LAR and AK contributed equally as co-first authors ABSTRACT elomerase is a ribonucleoprotein complex that maintains the length and integrity of telomeres, and thereby enables cellular proliferation. TUnderstanding the regulation of telomerase in hematopoietic cells is relevant to the pathogenesis of leukemia, in which telomerase is constitu- tively activated, as well as bone marrow failure syndromes that feature telomerase insufficiency. Past studies showing high levels of telomerase in human erythroblasts and a prevalence of anemia in disorders of telomerase insufficiency provide the rationale for investigating telomerase regulation in erythroid cells. -
Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation Hildur H
Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation Hildur H. Arnardottir, Jesmond Dalli, Lucy V. Norling, Romain A. Colas, Mauro Perretti and Charles N. Serhan This information is current as of September 27, 2021. J Immunol published online 17 August 2016 http://www.jimmunol.org/content/early/2016/08/17/jimmun ol.1502268 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2016/08/17/jimmunol.150226 Material 8.DCSupplemental Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 27, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published August 17, 2016, doi:10.4049/jimmunol.1502268 The Journal of Immunology Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation Hildur H. Arnardottir,* Jesmond Dalli,*,1 Lucy V. Norling,† Romain A. Colas,*,1 Mauro Perretti,† and Charles N. Serhan* Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis.