Anti-VAC14 (Aa 711-760) Polyclonal Antibody (CABT-BL5957) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use

Total Page：16

File Type：pdf, Size：1020Kb

Anti-VAC14 (aa 711-760) polyclonal antibody (CABT-BL5957) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Rabbit polyclonal antibody to Human VAC14. Antigen Description The content of phosphatidylinositol 3, 5-bisphosphate (PtdInsP2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. VAC14 is a component of a trimolecular complex that tightly regulates the level of PtdInsP2. Other components of this complex are the PtdInsP2-synthesizing enzyme PIKFYVE (MIM 609414) and the PtdInsP2 phosphatase FIG4 (MIM 609390). VAC14 functions as an activator of PIKFYVE (Sbrissa et al., 2007 Immunogen Synthetic peptide, corresponding to a region within C terminal amino acids 711-760 (QLLSHRLQCV PNPELLQTED SLKAAPKSQK ADSPSIDYAE LLQHFEKVQN) of Human VAC14. Isotype IgG Source/Host Rabbit Species Reactivity Human Purification Immunogen affinity purified Conjugate Unconjugated Sequence Similarities Belongs to the VAC14 family.Contains 6 HEAT repeats. Cellular Localization Endosome membrane. Microsome membrane. Mainly associated with membranes of the late endocytic pathway. Format Liquid Size 50 μg Buffer 97% PBS, 2% Sucrose Preservative None Storage Shipped at 4°C. Upon delivery aliquot and store at -20°C. Avoid repeated freeze/thaw cycles. 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved BACKGROUND Introduction The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. VAC14 is a component of a trimolecular complex that tightly regulates the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE (MIM 609414) and the PtdIns(3,5)P2 phosphatase FIG4 (MIM 609390). VAC14 functions as an activator of PIKFYVE (Sbrissa et al., 2007 [PubMed 17556371]).[supplied by OMIM, Feb 2010] GENE INFORMATION Entrez Gene ID 55697 Protein Refseq NP_060522 UniProt ID Q08AM6 Chromosome Location 16q22.1 Pathway HTLV-I infection, organism-specific biosystem; HTLV-I infection, conserved biosystem; Function binding; receptor activity; 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 2 © Creative Diagnostics All Rights Reserved.

Copy Link

Recommended publications

Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins.
[Show full text]
TMEM106B in Humans and Vac7 and Tag1 in Yeast Are Predicted to Be Lipid Transfer Proteins
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.12.435176; this version posted March 12, 2021. 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. TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins Tim P. Levine* UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, United Kingdom. ORCID 0000-0002-7231-0775 *Corresponding author and lead contact: [email protected] Data availability statement: The data that support this study are freely available in Harvard Dataverse at https://dataverse.harvard.edu/dataverse/LEA_2. Acknowledgements: work was funded by the Higher Education Funding Council for England and the NIHR Moorfields Biomedical Research Centre Conflict of interest disclosure: the author declares that there is no conflict of interest Keywords: Structural bioinformatics, Lipid transfer protein, LEA_2, TMEM106B, Vac7, YLR173W, Endosome, Lysosome Running Title: TMEM106B & Vac7: lipid transfer proteins 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.12.435176; this version posted March 12, 2021. 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 TMEM106B is an integral membrane protein of late endosomes and lysosomes involved in neuronal function, its over-expression being associated with familial frontotemporal lobar degeneration, and under-expression linked to hypomyelination. It has also been identified in multiple screens for host proteins required for productive SARS-CoV2 infection. Because standard approaches to understand TMEM106B at the sequence level find no homology to other proteins, it has remained a protein of unknown function.
[Show full text]
Biological Sciences—Genetics Human Genetic Variation in VAC14 Regulates Salmonella Invasion and Typhoid Feve
Classification: Biological Sciences—Genetics Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol 5 Monica I. Alvarez1, Luke C. Glover1, Peter Luo1, Liuyang Wang1, Elizabeth Theusch2, Stefan H. Oehlers1,3,4, Eric M. Walton1, Trinh Thi Bich Tram5, Yu-Lin Kuang2, Jerome I. Rotter6, Colleen M. McClean7, Nguyen Tran Chinh8, Marisa W. Medina2, David M. Tobin1,7, Sarah J. Dunstan9, Dennis C. Ko1,10 Affiliations: 10 1Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA. 2Children’s Hospital Oakland Research Institute, Oakland, CA 94609, USA. 3Tuberculosis Research Program, Centenary Institute, Camperdown, NSW 2050, Australia 4Sydney Medical School, The University of Sydney, Newtown, Australia 15 5Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. 6Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. 7Department of Immunology, School of Medicine, Duke University, Durham, NC 27710, USA. 20 8Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. 9Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia. 10Department of Medicine, School of Medicine, Duke University, Durham, NC 27710, USA. *To whom correspondence should be addressed: [email protected]. 25 1 Abstract Risk, severity, and outcome of infection depend on the
[Show full text]
Single Cell Spatial Chromatin Analysis of Fixed Immunocytochemically Identified Neuronal Cells
bioRxiv preprint doi: https://doi.org/10.1101/780387; this version posted September 24, 2019. 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: Single Cell Spatial Chromatin Analysis of Fixed Immunocytochemically Identified Neuronal Cells One Sentence Summary: A new method, CHEX-seq (CHromatin eXposed), identifies the open- chromatin landscape in single fixed cells thereby allowing spatial chromatin analysis of selected cells in complex cellular environments. Authors: Jaehee Lee1,#, Youtao Lu2,#, Jinchun Wang3,#, Jifen Li1, Stephen A. Fisher2, C. Erik Nordgren2, Jean G. Rosario2, Stewart A. Anderson4, Alexandra V. Ulyanova5, Steven Brem5, H. Isaac Chen5, John A. Wolf5, M. Sean Grady5, Mimi Healy3, Junhyong Kim2,& and James Eberwine1,&, % Affiliations: 1 Department of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA, 2 Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104 USA, 3 Agilent Technologies, Inc., 5301 Stevens Creek Blvd, Santa Clara, CA 95051, USA, 4 Department of Psychiatry, Children’s Hospital of Philadelphia, ARC 517, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA, 5Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. # These authors contributed equally to this manuscript. & These authors contributed equally to this manuscript. % Correspondence should be addressed to: James Eberwine, PhD University of Pennsylvania 37 John Morgan Building Philadelphia, PA 19104 [email protected] bioRxiv preprint doi: https://doi.org/10.1101/780387; this version posted September 24, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
[Show full text]
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.
[Show full text]
Human Genetic Variation Influences Enteric Fever Progression
cells Review Human Genetic Variation Influences Enteric Fever Progression Pei Yee Ma 1, Jing En Tan 2, Edd Wyn Hee 2, Dylan Wang Xi Yong 2, Yi Shuan Heng 2, Wei Xiang Low 2, Xun Hui Wu 2 , Christy Cletus 2, Dinesh Kumar Chellappan 3 , Kyan Aung 4, Chean Yeah Yong 5 and Yun Khoon Liew 3,* 1 School of Postgraduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia; [email protected] 2 School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia; [email protected] (J.E.T.); [email protected] (E.W.H.); [email protected] (D.W.X.Y.); [email protected] (Y.S.H.); [email protected] (W.X.L.); [email protected] (X.H.W.); [email protected] (C.C.) 3 Department of Life Sciences, International Medical University, Kuala Lumpur 57000, Malaysia; [email protected] 4 Department of Pathology, International Medical University, Kuala Lumpur 57000, Malaysia; [email protected] 5 Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia; [email protected] * Correspondence: [email protected] Abstract: In the 21st century, enteric fever is still causing a significant number of mortalities, espe- cially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to Citation: Ma, P.Y.; Tan, J.E.; Hee, and the severity of enteric fever. This review attempted to explain and discuss the past and the E.W.; Yong, D.W.X.; Heng, Y.S.; Low, W.X.; Wu, X.H.; Cletus, C.; Kumar most recent findings on human genetic variants affecting the progression of Salmonella typhoidal Chellappan, D.; Aung, K.; et al.
[Show full text]
VAC14 Gene‐Related Parkinsonism‐Dystonia with Response to Deep Brain Stimulation
de gusmao claudio (Orcid ID: 0000-0001-7171-1406) VAC14 gene-related parkinsonism-dystonia with response to deep brain stimulation Claudio M. de Gusmao, MD1, Scellig Stone, MD, PhD2, Jeff L. Waugh MD, PhD1,3, Edward Yang, MD, PhD4, Guy M. Lenk, PhD5, Lance H. Rodan, MD, FRCP(C)1,6 Affiliations: 1. Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 2. Department of Neurosurgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA 3. Division of Pediatric Neurology, University of Texas Southwestern, Dallas, Texas, USA 4. Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA 5. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA 6. Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Corresponding authors: Lance Rodan Boston Children's Hospital. 300 Longwood Ave. Boston, MA 02115 Phone: 857-218-4637 / Fax: 617-730-0466 Email: [email protected] This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/mdc3.12797 This article is protected by copyright. All rights reserved. Claudio Melo de Gusmao Boston Children’s Hospital. 300 Longwood Ave, Mailstop BCH 34343 Boston, MA 02115. Phone: 617-919-1412 / Fax: 617-730-0279 Email: [email protected] Word count: 800 words Running head title: VAC14 dystonia-parkinsonism responds to DBS Key words: Dystonia, Parkinsonism, Deep Brain Stimulation, Inborn genetic disease, Neurodegeneration with brain iron accumulation DISCLOSURES Funding sources and conflicts of interest: None of the authors have relevant financial disclosures or conflicts of interest directly relevant to this research.
[Show full text]
The P5-Atpase ATP13A1 Modulates MR1-Mediated Antigen Presentation
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.26.445708; this version posted May 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. The P5-ATPase ATP13A1 modulates MR1- mediated antigen presentation Corinna A. Kulicke1, Erica De Zan2, Zeynep Hein3, Claudia Gonzalez-Lopez1, Swapnil Ghanwat3, Natacha Veerapen4, Gurdyal S. Besra4, Paul Klenerman5,6, John C. Christianson7, Sebastian Springer3, Sebastian Nijman2, Vincenzo Cerundolo1, #, § , and Mariolina Salio1, # 1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK 2. Ludwig Institute for Cancer Research Ltd. and Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK 3. Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany. 4. School of Biosciences, University of Birmingham, Birmingham B11 2TT, United Kingdom 5. Peter Medawar Building, Nuffield Department of Medicine, University of Oxford 6. Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford 7. Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK # joint senior authors § deceased January 7th 2020 current addresses: C.K. – Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR, United States; S.N. – Scenic Biotech BV, Amsterdam, The Netherlands correspondence: [email protected]; [email protected] Keywords: MHC I-related protein 1 (MR1), mucosal-associated invariant T cell (MAIT), MR1-restricted T cell (MR1T), antigen presentation, protein trafficking, HAP1, gene trap, ATP13A1, P5-type ATPase bioRxiv preprint doi: https://doi.org/10.1101/2021.05.26.445708; this version posted May 27, 2021.
[Show full text]
VAC14 Syndrome in Two Siblings with Retinitis Pigmentosa and Neurodegeneration with Brain Iron Accumulation
COLD SPRING HARBOR Molecular Case Studies | RAPID COMMUNICATION VAC14 syndrome in two siblings with retinitis pigmentosa and neurodegeneration with brain iron accumulation Gholson J. Lyon,1 Elaine Marchi,1 Joseph Ekstein,2 Vardiella Meiner,3,4 Yoel Hirsch,2 Sholem Scher,2 Edward Yang,5 Darryl C. De Vivo,6 Ricardo Madrid,1 Quan Li,7 Kai Wang,8 Andrea Haworth,9 Ilana Chilton,10 Wendy K. Chung,10 and Milen Velinov1 1NYS Institute for Basic Research in Developmental Disabilities (IBR), Staten Island, New York 10314, USA; 2Dor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, Brooklyn, New York 11211, USA; 3Faculty of Medicine, Hebrew University, Jerusalem 9112001, Israel; 4Department of Genetics and Metabolic Diseases, Hadassah–Hebrew University Medical Center, Jerusalem 9112001, Israel; 5Department of Radiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA; 6Columbia University Irving Medical Center, The Neurological Institute, New York, New York 10032, USA; 7Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario M5G 2C1, Canada; 8Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; 9Congenica Ltd, Biodata Innovation Centre, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; 10Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York 10032, USA Abstract Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressing neurological disease present in two of six siblings with early childhood onset of severe progressive spastic paraparesis and learning disabilities. A homozygous mutation (c.2005G>T, p, V669L) was found in VAC14, and the clinical phenotype is consistent with the recently described VAC14-related striatonigral degeneration, childhood-onset syn- Corresponding authors: drome (SNDC) (MIM#617054).
[Show full text]
MAFB Determines Human Macrophage Anti-Inflammatory
MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis This information is current as of October 4, 2021. Víctor D. Cuevas, Laura Anta, Rafael Samaniego, Emmanuel Orta-Zavalza, Juan Vladimir de la Rosa, Geneviève Baujat, Ángeles Domínguez-Soto, Paloma Sánchez-Mateos, María M. Escribese, Antonio Castrillo, Valérie Cormier-Daire, Miguel A. Vega and Ángel L. Corbí Downloaded from J Immunol 2017; 198:2070-2081; Prepublished online 16 January 2017; doi: 10.4049/jimmunol.1601667 http://www.jimmunol.org/content/198/5/2070 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2017/01/15/jimmunol.160166 Material 7.DCSupplemental References This article cites 69 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/198/5/2070.full#ref-list-1 by guest on October 4, 2021 Why The JI? Submit online. • 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 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 © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606.
[Show full text]
Primepcr™Assay Validation Report
PrimePCR™Assay Validation Report Gene Information Gene Name Vac14 homolog (S. cerevisiae) Gene Symbol VAC14 Organism Human Gene Summary The content of phosphatidylinositol 35-bisphosphate (PtdIns(35)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. VAC14 is a component of a trimolecular complex that tightly regulates the level of PtdIns(35)P2. Other components of this complex are the PtdIns(35)P2-synthesizing enzyme PIKFYVE (MIM 609414) and the PtdIns(35)P2 phosphatase FIG4 (MIM 609390). VAC14 functions as an activator of PIKFYVE (Sbrissa et al. 2007 Gene Aliases ArPIKfyve, FLJ10305, FLJ36622, FLJ46582, MGC149815, MGC149816, TAX1BP2, TRX RefSeq Accession No. NC_000016.9, NT_010498.15 UniGene ID Hs.445061 Ensembl Gene ID ENSG00000103043 Entrez Gene ID 55697 Assay Information Unique Assay ID qHsaCED0042957 Assay Type SYBR® Green Detected Coding Transcript(s) ENST00000261776, ENST00000536184, ENST00000566416 Amplicon Context Sequence GTGGACCATGGTCGAGGCGAACTTGAGGTCCTCCTCCCGCAGCAGGATGTCTG CCATTGAGTGGAAGATGTTCTCCGCATTCAGCAGGAGGCACAGCTGCCTGA Amplicon Length (bp) 74 Chromosome Location 16:70732615-70765401 Assay Design Exonic Purification Desalted Validation Results Efficiency (%) 101 R2 0.9999 cDNA Cq 21.56 cDNA Tm (Celsius) 83.5 Page 1/5 PrimePCR™Assay Validation Report gDNA Cq 24.75 Specificity (%) 100 Information to assist with data interpretation is provided at the end of this report. Page 2/5 PrimePCR™Assay Validation Report VAC14, Human Amplification Plot
[Show full text]
TFEB Links MYC Signaling to Epigenetic Control of Myeloid Differentiation and Acute Myeloid Leukemia
RESEARCH ARTICLE TFEB Links MYC Signaling to Epigenetic Control of Myeloid Differentiation and Acute Myeloid Leukemia Seongseok Yun1, Nicole D. Vincelette1, Xiaoqing Yu2, Gregory W. Watson1, Mario R. Fernandez3, Chunying Yang3, Taro Hitosugi4, Chia-Ho Cheng2, Audrey R. Freischel3, Ling Zhang5, Weimin Li3, Hsinan Hou6, Franz X. Schaub3, Alexis R. Vedder1, Ling Cen2, Kathy L. McGraw1, Jungwon Moon1, Daniel J. Murphy7, Andrea Ballabio8,9,10,11,12, Scott H. Kaufmann4, Anders E. Berglund2, and John L. Cleveland3 Downloaded from https://bloodcancerdiscov.aacrjournals.org by guest on September 23, 2021. Copyright 2020 American Copyright 2021 by AssociationAmerican for Association Cancer Research. for Cancer Research. ABSTRACT MYC oncoproteins regulate transcription of genes directing cell proliferation, metabolism, and tumorigenesis. A variety of alterations drive MYC expression in acute myeloid leukemia (AML), and enforced MYC expression in hematopoietic progenitors is sufficient to induce AML. Here we report that AML and myeloid progenitor cell growth and survival rely on MYC- directed suppression of Transcription Factor EB (TFEB), a master regulator of the autophagy–lysosome pathway. Notably, although originally identified as an oncogene, TFEB functions as a tumor suppressor in AML, where it provokes AML cell differentiation and death. These responses reflect TFEB control of myeloid epigenetic programs by inducing expression of isocitrate dehydrogenase-1 (IDH1) and IDH2, resulting in global hydroxylation of 5-methycytosine. Finally, activating the TFEB–IDH1/IDH2–TET2 axis is revealed as a targetable vulnerability in AML. Thus, epigenetic control by an MYC–TFEB circuit dictates myeloid cell fate and is essential for maintenance of AML. SIGNIFIcaNCE: Alterations in epigenetic control are a hallmark of AML.
[Show full text]