Mouse APOBEC1 Cytidine Deaminase Can Induce
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Comprehensive Identification and Characterization of Somatic Copy Number Alterations in Triple‑Negative Breast Cancer
INTERNATIONAL JOURNAL OF ONCOLOGY 56: 522-530, 2020 Comprehensive identification and characterization of somatic copy number alterations in triple‑negative breast cancer ZAIBING LI1,2*, XIAO ZHANG3*, CHENXIN HOU4, YUQING ZHOU4, JUNLI CHEN1, HAOYANG CAI5, YIFENG YE3, JINPING LIU3 and NING HUANG1 1Department of Pathophysiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041; 2Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan 646000; 3Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731; 4West China Medical School, Sichuan University, Chengdu, Sichuan 610041; 5Center of Growth, Metabolism and Aging, Key Laboratory of Bio‑Resources and Eco‑Environment, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, P.R. China Received January 30, 2019; Accepted August 30, 2019 DOI: 10.3892/ijo.2019.4950 Abstract. Triple-negative breast cancer (TNBC) accounts hierarchical clustering of tumors resulted in three main for ~15% of all breast cancer diagnoses each year. Patients subgroups that exhibited distinct CNA profiles, which with TNBC tend to have a higher risk for early relapse and may reveal the heterogeneity of molecular mechanisms in a worse prognosis. TNBC is characterized by extensive TNBC subgroups. These results will extend the molecular somatic copy number alterations (CNAs). However, the DNA understanding of TNBC and will facilitate the discovery of CNA profile of TNBC remains to be extensively investigated. therapeutic and diagnostic target candidates. The present study assessed the genomic profile of CNAs in 201 TNBC samples, aiming to identify recurrent CNAs that Introduction may drive the pathogenesis of TNBC. -
Appendix 2. Significantly Differentially Regulated Genes in Term Compared with Second Trimester Amniotic Fluid Supernatant
Appendix 2. Significantly Differentially Regulated Genes in Term Compared With Second Trimester Amniotic Fluid Supernatant Fold Change in term vs second trimester Amniotic Affymetrix Duplicate Fluid Probe ID probes Symbol Entrez Gene Name 1019.9 217059_at D MUC7 mucin 7, secreted 424.5 211735_x_at D SFTPC surfactant protein C 416.2 206835_at STATH statherin 363.4 214387_x_at D SFTPC surfactant protein C 295.5 205982_x_at D SFTPC surfactant protein C 288.7 1553454_at RPTN repetin solute carrier family 34 (sodium 251.3 204124_at SLC34A2 phosphate), member 2 238.9 206786_at HTN3 histatin 3 161.5 220191_at GKN1 gastrokine 1 152.7 223678_s_at D SFTPA2 surfactant protein A2 130.9 207430_s_at D MSMB microseminoprotein, beta- 99.0 214199_at SFTPD surfactant protein D major histocompatibility complex, class II, 96.5 210982_s_at D HLA-DRA DR alpha 96.5 221133_s_at D CLDN18 claudin 18 94.4 238222_at GKN2 gastrokine 2 93.7 1557961_s_at D LOC100127983 uncharacterized LOC100127983 93.1 229584_at LRRK2 leucine-rich repeat kinase 2 HOXD cluster antisense RNA 1 (non- 88.6 242042_s_at D HOXD-AS1 protein coding) 86.0 205569_at LAMP3 lysosomal-associated membrane protein 3 85.4 232698_at BPIFB2 BPI fold containing family B, member 2 84.4 205979_at SCGB2A1 secretoglobin, family 2A, member 1 84.3 230469_at RTKN2 rhotekin 2 82.2 204130_at HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2 81.9 222242_s_at KLK5 kallikrein-related peptidase 5 77.0 237281_at AKAP14 A kinase (PRKA) anchor protein 14 76.7 1553602_at MUCL1 mucin-like 1 76.3 216359_at D MUC7 mucin 7, -
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. -
HPV16 and HPV18 Type-Specific APOBEC3 and Integration Profiles
medRxiv preprint doi: https://doi.org/10.1101/2020.11.25.20238477; this version posted November 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 1 HPV16 and HPV18 type-specific APOBEC3 and integration profiles in different 2 diagnostic categories of cervical samples 3 4 Sonja Lagström1,2,3, Alexander Hesselberg Løvestad4, Sinan Uğur Umu2, Ole Herman 5 Ambur4, Mari Nygård2, Trine B. Rounge2,6,#,*, Irene Kraus Christiansen1,7,#,*, 6 7 Author affiliations: 8 1 Department of Microbiology and Infection Control, Akershus University Hospital, 9 Lørenskog, Norway 10 2 Department of Research, Cancer Registry of Norway, Oslo, Norway 11 3 Institute of Clinical Medicine, University of Oslo, Oslo, Norway 12 4 Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo, Norway 13 5 Norwegian Cervical Cancer Screening Programme, Cancer Registry of Norway, Oslo, 14 Norway 15 6 Department of Informatics, University of Oslo, Oslo, Norway 16 7 Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus 17 University Hospital and University of Oslo, Lørenskog, Norway 18 19 20 #Equal contribution 21 *Corresponding authors 22 E-mail addresses: [email protected] (TBR), 23 [email protected] (IKC) 24 NOTE: This preprint reports new research that has not been certified1 by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.11.25.20238477; this version posted November 29, 2020. -
Mutator Catalogues and That the Proportion of CG Muta- Types
RESEARCH HIGHLIGHTS carcinoma. Moreover, the authors of APOBEC3B mRNA were generally GENOMICS found that 60–90% of mutations in higher, indicating that this is the these tumours affected CG base pairs, major mutator across the 13 cancer Mutator catalogues and that the proportion of CG muta- types. Using carcinogenic mutation tions correlated with the expression catalogues (such as the Cancer Gene of APOBEC3B across cancer types. Census and COSMIC) the authors Because APOBECs target cytosines found that APOBEC-signature within specific sequence contexts, mutations were prevalent in a subset the authors examined the cytosine of genes considered to be drivers of mutation signatures and found, for cancer, indicating that APOBEC- example, that those signatures in mediated mutation may initiate bladder and cervical cancers were and/or drive carcinogenesis. similar, and were biased towards the Taking a broader approach, optimum APOBEC3B motif (which Alexandrov and colleagues sought STOCKBYTE is TCA). The authors also found that to assess the mutational landscape bladder, cervical, head and neck, of >7,000 cancers, using exome and breast cancer, as well as lung and whole-genome sequence The sequencing of cancer genomes adenocarcinoma and lung squamous data. Their analyses revealed 21 has confirmed the complexity of cell carcinoma, all of which had distinct mutational signatures APOBEC3B is the somatic mutations that occur in the strongest APOBEC3B-specific that occurred, to different extents a mutator in tumours. However, there seem to cytosine mutation signatures, had the and in different combinations, be some patterns in the mutation highest levels of cytosine mutation across 30 cancer types. The most several types spectra, such as preference for muta- clustering. -
Expansions, Diversification, and Interindividual Copy Number
Expansions, diversification, and interindividual copy PNAS PLUS number variations of AID/APOBEC family cytidine deaminase genes in lampreys Stephen J. Hollanda,1, Lesley M. Berghuisb,1, Justin J. Kingb, Lakshminarayan M. Iyerc, Katarzyna Sikoraa, Heather Fifieldb, Sarah Petera,d, Emma M. Quinlanb, Fumiaki Sugaharae,f, Prashant Shingateg, Inês Trancosoa, Norimasa Iwanamia, Elena Temerevah, Christine Strohmeiera, Shigeru Kuratanie, Byrappa Venkateshg, Guillaume Evannoi, L. Aravindc, Michael Schorppa, Mani Larijanib,2, and Thomas Boehma,2,3 aMax Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; bProgram in Immunology and Infectious Diseases, Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada; cNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894; dLuxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-sur-Alzette, Luxembourg; eLaboratory for Evolutionary Morphology, RIKEN Center for Biosystems Dynamics Research, 650-0047 Kobe, Japan; fDivision of Biology, Hyogo College of Medicine, Nishinomiya, 663-8501 Hyogo, Japan; gComparative and Medical Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, 138673 Biopolis, Singapore; hBiological Faculty, Moscow State University, 119992 Moscow, Russia; and iEcology and Ecosystem Health, Institut National de la Recherche Agronomique, Agrocampus Ouest, 35042 Rennes, France Edited by Anjana Rao, La Jolla Institute and University of California, San Diego, La Jolla, CA, and approved February 27, 2018 (received for review November 30, 2017) Cytidine deaminases of the AID/APOBEC family catalyze C-to-U expansions, rapid evolution, and gene loss are also prevalent nucleotide transitions in mRNA or DNA. Members of the APOBEC3 evolutionary trends, suggesting a primary role for them in im- branch are involved in antiviral defense, whereas AID contributes mune responses (2). -
The Battle Between Retroviruses and APOBEC3 Genes: Its Past and Present
viruses Review The Battle between Retroviruses and APOBEC3 Genes: Its Past and Present Keiya Uriu 1,2,†, Yusuke Kosugi 3,4,†, Jumpei Ito 1 and Kei Sato 1,2,* 1 Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan; [email protected] (K.U.); [email protected] (J.I.) 2 Graduate School of Medicine, The University of Tokyo, Tokyo 1130033, Japan 3 Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; [email protected] 4 Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 6068501, Japan * Correspondence: [email protected]; Tel.: +81-3-6409-2212 † These authors contributed equally to this work. Abstract: The APOBEC3 family of proteins in mammals consists of cellular cytosine deaminases and well-known restriction factors against retroviruses, including lentiviruses. APOBEC3 genes are highly amplified and diversified in mammals, suggesting that their evolution and diversification have been driven by conflicts with ancient viruses. At present, lentiviruses, including HIV, the causative agent of AIDS, are known to encode a viral protein called Vif to overcome the antiviral effects of the APOBEC3 proteins of their hosts. Recent studies have revealed that the acquisition of an anti-APOBEC3 ability by lentiviruses is a key step in achieving successful cross-species transmission. Here, we summarize the current knowledge of the interplay between mammalian APOBEC3 proteins and viral infections and introduce a scenario of the coevolution of mammalian APOBEC3 genes and viruses. Keywords: APOBEC3; lentivirus; Vif; arms race; gene diversification; coevolution Citation: Uriu, K.; Kosugi, Y.; Ito, J.; Sato, K. -
Deaminase-Independent Mode of Antiretroviral Action in Human and Mouse APOBEC3 Proteins
microorganisms Review Deaminase-Independent Mode of Antiretroviral Action in Human and Mouse APOBEC3 Proteins Yoshiyuki Hakata 1,* and Masaaki Miyazawa 1,2 1 Department of Immunology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan; [email protected] 2 Kindai University Anti-Aging Center, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan * Correspondence: [email protected]; Tel.: +81-72-367-7660 Received: 8 December 2020; Accepted: 9 December 2020; Published: 12 December 2020 Abstract: Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins (APOBEC3s) are deaminases that convert cytosines to uracils predominantly on a single-stranded DNA, and function as intrinsic restriction factors in the innate immune system to suppress replication of viruses (including retroviruses) and movement of retrotransposons. Enzymatic activity is supposed to be essential for the APOBEC3 antiviral function. However, it is not the only way that APOBEC3s exert their biological function. Since the discovery of human APOBEC3G as a restriction factor for HIV-1, the deaminase-independent mode of action has been observed. At present, it is apparent that both the deaminase-dependent and -independent pathways are tightly involved not only in combating viruses but also in human tumorigenesis. Although the deaminase-dependent pathway has been extensively characterized so far, understanding of the deaminase-independent pathway remains immature. Here, we review existing knowledge regarding the deaminase-independent antiretroviral functions of APOBEC3s and their molecular mechanisms. We also discuss the possible unidentified molecular mechanism for the deaminase-independent antiretroviral function mediated by mouse APOBEC3. Keywords: APOBEC3; deaminase-independent antiretroviral function; innate immunity 1. -
1 APOBEC-Mediated Mutagenesis in Urothelial Carcinoma Is Associated
bioRxiv preprint doi: https://doi.org/10.1101/123802; this version posted April 4, 2017. 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. APOBEC-mediated mutagenesis in urothelial carcinoma is associated with improved survival, mutations in DNA damage response genes, and immune response Alexander P. Glaser MD, Damiano Fantini PhD, Kalen J. Rimar MD, Joshua J. Meeks MD PhD APG, DF, KJR, JJM: Northwestern University, Department of Urology, Chicago, IL, 60607 Running title: APOBEC mutagenesis in bladder cancer *Corresponding author: Joshua J. Meeks, MD PhD 303 E. Chicago Ave. Tarry 16-703 Chicago, IL 60611 Email: [email protected] Keywords (4-6): • Urinary bladder neoplasms • APOBEC Deaminases • Mutagenesis • DNA damage • Interferon Abbreviations and Acronyms: TCGA – The Cancer Genome Atlas ssDNA – single stranded DNA APOBEC –apolipoprotein B mRNA editing catalytic polypeptide-like GCAC – Genome Data Analysis Center MAF – mutation annotation format “APOBEC-high” – tumors enriched for APOBEC mutagenesis “APOBEC-low” – tumors not enriched for APOBEC mutagenesis 1 bioRxiv preprint doi: https://doi.org/10.1101/123802; this version posted April 4, 2017. 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. Abstract: Background: The APOBEC family of enzymes is responsible for a mutation signature characterized by a TCW>T/G mutation. APOBEC-mediated mutagenesis is implicated in a wide variety of tumors, including bladder cancer. In this study, we explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival. -
Targeted Cancer Therapy Induces APOBEC Fuelling the Evolution of Drug Resistance Authors: Manasi K
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.18.423280; this version posted December 18, 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. Title: Targeted cancer therapy induces APOBEC fuelling the evolution of drug resistance Authors: Manasi K. Mayekara†, Deborah R. Caswellb*†, Natalie I. Vokesc-d, Emily K. Lawe-h, Wei Wua, William Hillb, Eva Gronroosb, Andrew Rowanb, Maise Al Bakirb, Caroline E. McCoacha, Collin M. Blakelya, Nuri Alpay Temizi, Ai Naganob, D. Lucas Kerra, Julia K. Rotowj, Franziska Haderka, Michelle Dietzenk,r, Carlos Martinez Ruizk,r, Bruna Almeidal, Lauren Cecha, Beatrice Ginia, Joanna Przewrockab, Chris Moorem, Miguel Murillom, Bjorn Bakkerb, Brandon Ruleb, Cameron Durfeee-g, Shigeki Nanjoa, Lisa Tana, Lindsay K. Larsone-g, Prokopios P. Argyrise-h,n, William L. Browne-g, Johnny Yuo, Carlos Gomeza, Philippe Guia, Rachel I. Vogelf,p, Elizabeth A. Yua, Nicholas J. Thomasa, Subramanian Venkatesanb,r, Sebastijan Hoborb, Su Kit Chewr, Nnennaya Kanur, Nicholas McGranahank,r, Eliezer M. Van Allenq, Julian Downwardm, Reuben S. Harrise-h, Trever G. Bivonaa*, Charles Swantonb,r Affiliations: aDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA bCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK cDepartment of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas dDepartment -
Insights Into the Structures and Multimeric Status of APOBEC Proteins Involved in Viral Restriction and Other Cellular Functions
viruses Review Insights into the Structures and Multimeric Status of APOBEC Proteins Involved in Viral Restriction and Other Cellular Functions Xiaojiang S. Chen 1,2,3 1 Molecular and Computational Biology, Departments of Biological Sciences, Chemistry, University of Southern California, Los Angeles, CA 90089, USA; [email protected]; Tel.: +1-213-740-5487 2 Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA 3 Center of Excellence in NanoBiophysics/Structural Biology, University of Southern California, Los Angeles, CA 90089, USA Abstract: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of deaminase proteins that can catalyze the deamination of cytosine to uracil on single- stranded DNA or/and RNA. APOBEC proteins are involved in diverse biological functions, including adaptive and innate immunity, which are critical for restricting viral infection and endogenous retroelements. Dysregulation of their functions can cause undesired genomic mutations and RNA modification, leading to various associated diseases, such as hyper-IgM syndrome and cancer. This review focuses on the structural and biochemical data on the multimerization status of individual APOBECs and the associated functional implications. Many APOBECs form various multimeric complexes, and multimerization is an important way to regulate functions for some of these proteins at several levels, such as deaminase activity, protein stability, subcellular localization, protein storage Citation: Chen, X.S. Insights into and activation, virion packaging, and antiviral activity. The multimerization of some APOBECs is the Structures and Multimeric Status more complicated than others, due to the associated complex RNA binding modes. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase.