ATXN3

Summary

Gene Symbol: ATXN3
Description: ataxin 3
Alias: AT3, ATX3, JOS, MJD, MJD1, SCA3, ataxin-3, Machado-Joseph disease protein 1, josephin, olivopontocerebellar ataxia 3, spinocerebellar ataxia type 3 protein
Species: human

Top Publications

  1. ncbi CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1
    Y Kawaguchi
    Department of Pharmacology, Kyoto University Faculty of Medicine, Japan
    Nat Genet 8:221-8. 1994
  2. pmc Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis
    Yaohui Chai
    Department of Neurology, 3160 Medical Labs, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 99:9310-5. 2002
  3. ncbi Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature
    Stephane Marchal
    INSERM U128, IFR 122, 1919 Route de Mende, F 34293 Montpellier cedex 5, France
    J Biol Chem 278:31554-63. 2003
  4. ncbi Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease
    Y R Wu
    Second Department of Neurology, Chang Gung Memorial Hospital, Taipei, Taiwan
    Clin Genet 65:209-14. 2004
  5. ncbi A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration
    Daniel Goti
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neurosci 24:10266-79. 2004
  6. pmc A major role for side-chain polyglutamine hydrogen bonding in irreversible ataxin-3 aggregation
    Antonino Natalello
    Department of Biotechnologies and Biosciences, University of Milano Bicocca, Milan, Italy
    PLoS ONE 6:e18789. 2011
  7. ncbi Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3
    J L Griffin
    Department of Biochemistry, University of Cambridge, United Kingdom
    Physiol Genomics 16:334-40. 2004
  8. doi FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3
    Julieta Araujo
    Department of Neurology, University of Bonn, 53105 Bonn, Germany
    Hum Mol Genet 20:2928-41. 2011
  9. ncbi Ataxin-3 represses transcription via chromatin binding, interaction with histone deacetylase 3, and histone deacetylation
    Bernd O Evert
    Department of Neurology, University of Bonn, 53105 Bonn, Germany
    J Neurosci 26:11474-86. 2006
  10. doi The role of the central flexible region on the aggregation and conformational properties of human ataxin-3
    Carlo Santambrogio
    Department of Biotechnology and Biosciences, University of Milano Bicocca, Milan, Italy
    FEBS J 279:451-63. 2012

Research Grants

  1. Triplet Repeat Disease:Requirement for Caspase Cleavage
    Lisa Ellerby; Fiscal Year: 2007
  2. MECHANISMS OF POLYGLUTAMINE NEUROTOXICITY
    William Herring; Fiscal Year: 1999
  3. Tapas K Hazra; Fiscal Year: 2016
  4. Structures and functions of the human Josephin domain-containing proteins
    Patrick J Loll; Fiscal Year: 2012
  5. GULIN OZ; Fiscal Year: 2014
  6. Dietary Factors Affecting Calcium and Zinc Absorption
    Steven Abrams; Fiscal Year: 2006
  7. Norma C Ware; Fiscal Year: 2014
  8. DAVID OLUFEMI OLALEYE; Fiscal Year: 2015
  9. Northwestern University AITRP
    Robert L Murphy; Fiscal Year: 2012
  10. Emmanuel Idigbe; Fiscal Year: 2015

Detail Information

Publications229 found, 100 shown here

  1. ncbi CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1
    Y Kawaguchi
    Department of Pharmacology, Kyoto University Faculty of Medicine, Japan
    Nat Genet 8:221-8. 1994
    ..1, the genetic locus for Machado-Joseph disease (MJD)...
  2. pmc Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis
    Yaohui Chai
    Department of Neurology, 3160 Medical Labs, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 99:9310-5. 2002
    ....
  3. ncbi Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature
    Stephane Marchal
    INSERM U128, IFR 122, 1919 Route de Mende, F 34293 Montpellier cedex 5, France
    J Biol Chem 278:31554-63. 2003
    ..Several intermediate structures were detected in this process. Two factors appear to govern ataxin unfolding and aggregation, the length of the polyglutamine tract and its protein context...
  4. ncbi Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease
    Y R Wu
    Second Department of Neurology, Chang Gung Memorial Hospital, Taipei, Taiwan
    Clin Genet 65:209-14. 2004
    ..MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%)...
  5. ncbi A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration
    Daniel Goti
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neurosci 24:10266-79. 2004
    Machado-Joseph disease (MJD) is an inherited neurodegenerative disorder caused by ataxin-3 with a polyglutamine expansion...
  6. pmc A major role for side-chain polyglutamine hydrogen bonding in irreversible ataxin-3 aggregation
    Antonino Natalello
    Department of Biotechnologies and Biosciences, University of Milano Bicocca, Milan, Italy
    PLoS ONE 6:e18789. 2011
    The protein ataxin-3 consists of an N-terminal globular Josephin domain (JD) and an unstructured C-terminal region containing a stretch of consecutive glutamines that triggers the neurodegenerative disorder spinocerebellar ataxia type 3, ..
  7. ncbi Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3
    J L Griffin
    Department of Biochemistry, University of Cambridge, United Kingdom
    Physiol Genomics 16:334-40. 2004
    ..b>SCA3 or Machado-Joseph disease (MJD) is the commonest dominant inherited ataxia disease, with pathological phenotypes ..
  8. doi FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3
    Julieta Araujo
    Department of Neurology, University of Bonn, 53105 Bonn, Germany
    Hum Mol Genet 20:2928-41. 2011
    Ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3), binds to target gene promoters and modulates transcription by interaction with transcriptional regulators...
  9. ncbi Ataxin-3 represses transcription via chromatin binding, interaction with histone deacetylase 3, and histone deacetylation
    Bernd O Evert
    Department of Neurology, University of Bonn, 53105 Bonn, Germany
    J Neurosci 26:11474-86. 2006
    Ataxin-3 (AT3), the disease protein in spinocerebellar ataxia type 3 (SCA3), has been associated with the ubiquitin-proteasome system and transcriptional regulation...
  10. doi The role of the central flexible region on the aggregation and conformational properties of human ataxin-3
    Carlo Santambrogio
    Department of Biotechnology and Biosciences, University of Milano Bicocca, Milan, Italy
    FEBS J 279:451-63. 2012
    ..This protein consists of a folded N-terminal domain (Josephin domain, residues 1-182), a central flexible region (residues 183-291), a poly-glutamine sequence of variable ..
  11. ncbi Elucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics
    Hartmut Scheel
    Bioinformatics Group, Memorec Biotec GmbH, Koln, Germany
    Hum Mol Genet 12:2845-52. 2003
    ..Ataxin-3, the protein mutated in Machado Joseph Disease (SCA3), belongs to a novel group of cysteine-proteases and is predicted to be active against ubiquitin chains or related ..
  12. ncbi Sequence-dependent and independent inhibition specific for mutant ataxin-3 by small interfering RNA
    Yi Li
    Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Ann Neurol 56:124-9. 2004
    In Machado-Joseph disease (MJD) gene, there is a C/G polymorphism immediately after the CAG repeat; the expanded CAG repeat tract is exclusively followed by C, whereas about half of wild-type alleles are followed by G...
  13. ncbi Dynamic expression of Hsp27 in the presence of mutant ataxin-3
    Wei Hsiu Chang
    Department of Life Science, Tunghai University, Taichung, Taiwan
    Biochem Biophys Res Commun 336:258-67. 2005
    Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant spinocerebellar degeneration characterized by a wide range of clinical manifestations...
  14. pmc The Josephin domain determines the morphological and mechanical properties of ataxin-3 fibrils
    Laura Masino
    Division of Molecular Structure, Medical Research Council, National Institute for Medical Research, London, United Kingdom
    Biophys J 100:2033-42. 2011
    ..of the nonpathological form of ataxin-3, carrying an unexpanded polyQ tract, are modulated by its N-terminal Josephin domain...
  15. pmc Valosin-containing protein (VCP/p97) is an activator of wild-type ataxin-3
    Mario N Laco
    Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
    PLoS ONE 7:e43563. 2012
    ..disease (MJD) or Spinocerebellar Ataxia type 3 is caused by a polyglutamine-encoding CAG expansion in the ATXN3 gene, which encodes a 42 kDa deubiquitinating enzyme (DUB), ataxin-3...
  16. doi Calpain-mediated ataxin-3 cleavage in the molecular pathogenesis of spinocerebellar ataxia type 3 (SCA3)
    Jeannette Hübener
    Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen 72076, Germany
    Hum Mol Genet 22:508-18. 2013
    Spinocerebellar ataxia type 3 (SCA3) is pathologically characterized by the formation of intranuclear aggregates which contain ataxin-3, the mutated protein in SCA3, in a specific subtype of neurons...
  17. ncbi Molecular analysis of CAG repeats at five different spinocerebellar ataxia loci: correlation and alternative explanations for disease pathogenesis
    Ravindra Varma Alluri
    Department of Genetics and Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad 500 068, A P, India
    Mol Cells 24:338-42. 2007
    ..The sizes and distributions of repeats at the SCA1, SCA2, SCA3, SCA7 and DRPLA loci were assessed by molecular analysis of 124 unrelated ataxia patients and 44 controls, and the ..
  18. ncbi Machado-Joseph disease gene products carrying different carboxyl termini
    J Goto
    Department of Neurology, Institute for Brain Research, Faculty of Medicine, University of Tokyo, Japan
    Neurosci Res 28:373-7. 1997
    Three cDNA clones for the Machado-Joseph disease gene (MJD1) were isolated, two of which have a new exon sequence and a distinct 3' terminal nucleotide sequence resulting in a new carboxyl terminal domain in the translated product...
  19. ncbi Ataxin-3 is transported into the nucleus and associates with the nuclear matrix
    D Tait
    Max Planck Institut fur Molekulare Genetik, Ihnestrasse 73, D 14195 Berlin Dahlem, Germany
    Hum Mol Genet 7:991-7. 1998
    ..Our results taken together with the finding of a nuclear localization signal in ataxin-3 indicate that the ataxin-3 protein per se translocates to the nucleus and that an expanded glutamine repeat is not essential for this transport...
  20. ncbi Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B
    G Wang
    Laboratory for CAG Repeat Diseases, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama, 351 0198, Japan
    Hum Mol Genet 9:1795-803. 2000
    ..dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3...
  21. pmc Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates
    Kathryn M Donaldson
    Department of Cancer and Cell Biology, Genomics Institute of the Novartis Research Foundation GNF, 10675 John J Hopkins Drive, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 100:8892-7. 2003
    ..We propose that the Ub-mediated sequestration of essential Ub-binding protein(s) into aggregates may be a common mechanism contributing to the pathogenesis of neurodegenerative diseases...
  22. ncbi Domain architecture of the polyglutamine protein ataxin-3: a globular domain followed by a flexible tail
    Laura Masino
    National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
    FEBS Lett 549:21-5. 2003
    ..Moreover, [(15)N]glutamine selectively labelled samples allowed us to have a direct insight by NMR into the structure of the polyQ region...
  23. ncbi Structural and functional analysis of ataxin-2 and ataxin-3
    Mario Albrecht
    Max Planck Institute for Informatics, Saarbrucken, Germany
    Eur J Biochem 271:3155-70. 2004
    ..the construction of tertiary structure models of the RNA-binding Lsm domain of ataxin-2 and the deubiquitinating Josephin domain of ataxin-3...
  24. ncbi Research on screening and identification of proteins interacting with ataxin-3
    Lu Shen
    Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 22:242-7. 2005
    ..the proteins that interact with ataxin-3, to confirm the interacted domain, and to provide new clues for exploring the function of ataxin-3 and the pathogenesis of spinocerebellar ataxia type 3 and Machado-Joseph disease (SCA3/MJD).
  25. ncbi Evidence for distinct functions for human DNA repair factors hHR23A and hHR23B
    Li Chen
    Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    FEBS Lett 580:3401-8. 2006
    ..We also determined that hHR23A and hHR23B could be co-purified with unique proteolytic and stress-responsive factors from human breast cancer tissues, indicating that they have unique functions in vivo...
  26. doi Josephin domain of ataxin-3 contains two distinct ubiquitin-binding sites
    Giuseppe Nicastro
    National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
    Biopolymers 91:1203-14. 2009
    ..The enzymatic site resides in the N-terminal josephin domain of ataxin-3...
  27. pmc Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3
    Joonil Jung
    Department of Biology and University of Pennsylvania, Philadelphila, PA 19104 6018, USA
    Hum Mol Genet 18:4843-52. 2009
    ..Ataxin-3 protein with an expanded polyglutamine (polyQ) repeat causes spinocerebellar ataxia type-3 (SCA3), also called Machado-Joseph disease, and is cleaved in mammalian cells, transgenic mice and SCA3 patient brain ..
  28. ncbi Identification of three novel polymorphisms in the MJD1 gene and study of their frequency in the Portuguese population
    Maria do Carmo Costa
    UnIGENe, IBMC, Universidade do Porto, Portugal
    J Hum Genet 47:205-7. 2002
    ..is an autosomal dominant neurodegenerative disorder of late onset, caused by the expansion of a (CAG)n tract in the MJD1 gene...
  29. ncbi Poly-ubiquitin binding by the polyglutamine disease protein ataxin-3 links its normal function to protein surveillance pathways
    Yaohui Chai
    Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242 1101, USA
    J Biol Chem 279:3605-11. 2004
    ..markedly influenced by the surrounding protein context; ataxin-3 that lacks the highly conserved, amino-terminal josephin domain shows significantly faster association and dissociation rates for tetra-ubiquitin binding...
  30. pmc A mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice
    Veronica F Colomer Gould
    Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer Research Building, Room 4 158, Baltimore, MD 21287, USA
    Neurobiol Dis 27:362-9. 2007
    Machado-Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3)...
  31. ncbi Suppression of polyglutamine toxicity by the yeast Sup35 prion domain in Drosophila
    Ling Bo Li
    Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104 6018, USA
    J Biol Chem 282:37694-701. 2007
    ..the relationship between the pathogenic ataxin-3 protein of the human disease spinocerebellar ataxia type 3 (SCA3) and the yeast prion Sup35, using Drosophila as a model system...
  32. pmc RNA toxicity is a component of ataxin-3 degeneration in Drosophila
    Ling Bo Li
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6018, USA
    Nature 453:1107-11. 2008
    ..In a Drosophila screen for modifiers of polyQ degeneration induced by the spinocerebellar ataxia type 3 (SCA3) protein ataxin-3, we isolated an upregulation allele of muscleblind (mbl), a gene implicated in the RNA toxicity ..
  33. pmc The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains
    Brett J Winborn
    Department of Neurology, University of Michigan, Ann Arbor, Michigan 48108, USA
    J Biol Chem 283:26436-43. 2008
    ..Ataxin-3 cleaves ubiquitin chains through its amino-terminal Josephin domain and binds ubiquitin chains through a carboxyl-terminal cluster of ubiquitin interaction motifs neighboring ..
  34. pmc Proteotoxic stress increases nuclear localization of ataxin-3
    Christopher P Reina
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Hum Mol Genet 19:235-49. 2010
    ..Mapping studies showed that two regions of Atx3, the Josephin domain and the C-terminus, regulated heat shock-induced nuclear localization...
  35. pmc Functional interactions as a survival strategy against abnormal aggregation
    Laura Masino
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    FASEB J 25:45-54. 2011
    ..solubility and aggregation rates of ataxin-3, but these properties are profoundly modulated by its N-terminal Josephin domain...
  36. pmc Understanding the role of the Josephin domain in the PolyUb binding and cleavage properties of ataxin-3
    Giuseppe Nicastro
    National Institute for Medical Research, Medical Research Council, London, United Kingdom
    PLoS ONE 5:e12430. 2010
    ..which it anchors polyubiquitin chains of different linkages that are then cleaved by the N-terminal catalytic (Josephin) domain...
  37. pmc The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability
    Thomas M Durcan
    Centre for Neuronal Survival and McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    Hum Mol Genet 20:141-54. 2011
    Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3...
  38. pmc Splice isoforms of the polyglutamine disease protein ataxin-3 exhibit similar enzymatic yet different aggregation properties
    Ginny Marie Harris
    Graduate Program in Molecular and Cellular Biology, University of Iowa, Iowa City, Iowa, United States of America
    PLoS ONE 5:e13695. 2010
    ..Ataxin-3, a deubiquitinating enzyme and the disease protein in SCA3, is alternatively spliced to encode either a C-terminal hydrophobic stretch or a third ubiquitin interacting motif (..
  39. pmc Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme
    Thomas M Durcan
    Department of Neurology and Neurosurgery, Centre for Neuronal Survival and McGill Parkinson Program, Montreal Neurological Institute, Montreal, Quebec, Canada
    J Biol Chem 287:531-41. 2012
    ....
  40. doi Temperature profoundly affects ataxin-3 fibrillogenesis
    Alessandra Apicella
    Department of Energy and NEMAS, Center for NanoEngineered Materials and Surfaces, Politecnico di Milano, via Ponzio 34 3 I 20133 Milano, Italy
    Biochimie 94:1026-31. 2012
    Ataxin-3 (AT3) triggers spinocerebellar ataxia type 3 when it carries a polyglutamine stretch expanded beyond a critical threshold...
  41. ncbi Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients
    L Schols
    Department of Neurology, St Josef Hospital, Bochum, Germany
    Hum Mol Genet 4:1001-5. 1995
    ..The MJD1 gene has recently been cloned and the disease causing mutation has been identified as an unstable and expanded (CAG)..
  42. ncbi The gene for Machado-Joseph disease maps to human chromosome 14q
    Y Takiyama
    Department of Neurology, Jichi Medical School, Tochigi, Japan
    Nat Genet 4:300-4. 1993
    Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems...
  43. ncbi Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo
    H Ikeda
    Department of Pharmacology, Kyoto University Faculty of Medicine, Japan
    Nat Genet 13:196-202. 1996
    Recently, we identified a novel gene, MJD1, which contains an expanded CAG triplet repeat in Machado-Joseph disease...
  44. ncbi Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain
    H L Paulson
    Department of Pharmacology, University of Pennsylvania, Philadelphia 19104, USA
    Ann Neurol 41:453-62. 1997
    ..To study the molecular mechanism of disease, we isolated both normal and expanded repeat MJD1 cDNAs, and generated antiserum against the recombinant gene product, called ataxin-3...
  45. ncbi The genomic structure and expression of MJD, the Machado-Joseph disease gene
    Y Ichikawa
    Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
    J Hum Genet 46:413-22. 2001
    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder that is clinically characterized by cerebellar ataxia and various associated symptoms...
  46. ncbi Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities
    Fusheng Li
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    J Biol Chem 277:45004-12. 2002
    ....
  47. pmc Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis
    Ellen W Doss-Pepe
    Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA
    Mol Cell Biol 23:6469-83. 2003
    ....
  48. ncbi The polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity
    Barrington Burnett
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104 6084, USA
    Hum Mol Genet 12:3195-205. 2003
    ..Data in the present study suggest that the polyglutamine neurodegenerative disease protein, ataxin-3 (AT3), functions in the ubiquitin-proteasome pathway...
  49. ncbi Destabilization of a non-pathological variant of ataxin-3 results in fibrillogenesis via a partially folded intermediate: a model for misfolding in polyglutamine disease
    Michelle K M Chow
    Department of Biochemistry and Molecular Biology, Structural Biology Group, Monash University, Clayton Campus, PO Box 13D, Wellington Rd, 3800, Clayton, Vic, Australia
    J Mol Biol 335:333-41. 2004
    ..The implications of this are considered in the wider context of the development and pathogenesis of polyglutamine diseases...
  50. ncbi Temperature-dependent, irreversible formation of amyloid fibrils by a soluble human ataxin-3 carrying a moderately expanded polyglutamine stretch (Q36)
    Erlet Shehi
    Dipartimento di Biotecnologie e Bioscienze, Universita di Milano Bicocca, Piazza della Scienza 2, I 20126 Milano, Italy
    Biochemistry 42:14626-32. 2003
    ..Finally, we suggest that antiamyloidogenic compounds might be selected on the basis of their ability to block or retard human Q36 ataxin-3 precipitation on heat-treatment...
  51. pmc Molecular clearance of ataxin-3 is regulated by a mammalian E4
    Masaki Matsumoto
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    EMBO J 23:659-69. 2004
    ..in which the abnormal expansion of a polyglutamine tract is responsible for spinocerebellar ataxia type 3 (SCA3), undergoes ubiquitylation and degradation by the proteasome...
  52. ncbi Caspase-mediated proteolysis of the polyglutamine disease protein ataxin-3
    Sarah J Shoesmith Berke
    Neuroscience Graduate Program and Department of Neurology, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurochem 89:908-18. 2004
    ..Finally, caspase-mediated cleavage of expanded ataxin-3 resulted in increased ataxin-3 aggregation, suggesting a potential role for caspase-mediated proteolysis in spinocerebellar ataxia type-3 pathogenesis...
  53. ncbi Polyglutamine expansion in ataxin-3 does not affect protein stability: implications for misfolding and disease
    Michelle K M Chow
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
    J Biol Chem 279:47643-51. 2004
    ..Furthermore, given that native state stability is unaffected by polyglutamine length, we consider the possible role and influence of other factors in the fibrillization of ataxin-3...
  54. ncbi Assignment of the 1H, 13C, and 15N resonances of the Josephin domain of human ataxin-3
    Giuseppe Nicastro
    J Biomol NMR 30:457-8. 2004
  55. pmc The polyglutamine neurodegenerative protein ataxin 3 regulates aggresome formation
    Barrington G Burnett
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Proc Natl Acad Sci U S A 102:4330-5. 2005
    The polyglutamine-containing neurodegenerative protein ataxin 3 (AT3) has deubiquitylating activity and binds ubiquitin chains with a preference for chains of four or more ubiquitins...
  56. ncbi Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism
    John M Warrick
    Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 18:37-48. 2005
    ..function and disease pathogenesis to ubiquitin pathways in the polyglutamine disease spinocerebellar ataxia type 3 (SCA3)...
  57. ncbi Defining the role of ubiquitin-interacting motifs in the polyglutamine disease protein, ataxin-3
    Sarah J Shoesmith Berke
    Neuroscience Graduate Program, University of Iowa, Iowa City 52242, USA
    J Biol Chem 280:32026-34. 2005
    ....
  58. pmc Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain
    Yuxin Mao
    Howard Hughes Medical Institute and Department of Cell Biology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 102:12700-5. 2005
    ..The affected protein, ataxin-3, which contains an N-terminal Josephin domain followed by tandem ubiquitin (Ub)-interacting motifs (UIMs) and a polyglutamine stretch, has been ..
  59. ncbi Towards a structural understanding of the fibrillization pathway in Machado-Joseph's disease: trapping early oligomers of non-expanded ataxin-3
    Luis Gales
    ICBAS Instituto de Ciências Biomédicas de Abel Salazar and IBMC Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
    J Mol Biol 353:642-54. 2005
    ..accompanied by an increase in beta-structure; and (b) the first intermediate in the oligomerization pathway is a Josephin domain-mediated dimer of ataxin-3...
  60. pmc An arginine/lysine-rich motif is crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis
    Annett Boeddrich
    Department of Neuroproteomics, Max Delbrueck Center for Molecular Medicine MDC, Berlin, Germany
    EMBO J 25:1547-58. 2006
    ..Together, these results define the VCP-Atx-3 association as a potential target for therapeutic intervention and suggest that it might influence the progression of spinocerebellar ataxia type 3...
  61. ncbi The two-stage pathway of ataxin-3 fibrillogenesis involves a polyglutamine-independent step
    Andrew M Ellisdon
    Department of Biochemistry and Molecular Biology, Monash University, P O Box 13D, Wellington Road, Clayton, Victoria 3800, Australia
    J Biol Chem 281:16888-96. 2006
    ..However, the mechanism of aggregation is currently not well understood. Ataxin-3 consists of a folded Josephin domain followed by two ubiquitin-interacting motifs and a C-terminal polyglutamine tract, which in the non-..
  62. ncbi Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates
    Xiaoyan Zhong
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Hum Mol Genet 15:2409-20. 2006
    Expansion of a polyglutamine tract in ataxin-3 (AT3) results in spinocerebellar ataxia type 3/Machado-Joseph disease, one of the nine polyglutamine neurodegenerative diseases...
  63. pmc Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 174:963-71. 2006
    ..We report that efficient elimination of misfolded ER proteins also involves ataxin-3 (atx3), a p97-associated deubiquitinating enzyme mutated in type-3 spinocerebellar ataxia...
  64. ncbi p45, an ATPase subunit of the 19S proteasome, targets the polyglutamine disease protein ataxin-3 to the proteasome
    Hongfeng Wang
    Hefei National Laboratory for Physical Sciences at Microscale and Department of Neurobiology, School of Life Sciences, University of Science and Technology of China, PR China
    J Neurochem 101:1651-61. 2007
    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD-1 gene product, ataxin-3. Ataxin-3 is degraded by the proteasome...
  65. ncbi Phosphorylation of ataxin-3 by glycogen synthase kinase 3beta at serine 256 regulates the aggregation of ataxin-3
    Erkang Fei
    Hefei National Laboratory for Physical Sciences at Microscale and Department of Neurobiology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People s Republic of China
    Biochem Biophys Res Commun 357:487-92. 2007
    Machado-Joseph disease (MJD) is a dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract in MJD-1 gene product, ataxin-3...
  66. ncbi Calpain inhibition is sufficient to suppress aggregation of polyglutamine-expanded ataxin-3
    Annette Haacke
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    J Biol Chem 282:18851-6. 2007
    ..These findings suggest a critical role of calpains in the pathogenesis of Spinocerebellar ataxia type 3...
  67. ncbi Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence
    Ulrike Bichelmeier
    Department of Medical Genetics, University of Tubingen, D 72076 Tubingen, Germany
    J Neurosci 27:7418-28. 2007
    Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited neurodegenerative disorder caused by the expansion of a CAG repeat in the MJD1 gene resulting in an expanded polyglutamine repeat in the ataxin-3 protein...
  68. ncbi Cellular turnover of the polyglutamine disease protein ataxin-3 is regulated by its catalytic activity
    Sokol V Todi
    Department of Neurology, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 282:29348-58. 2007
    ..Taken together, these and other findings suggest that the catalytic activity of this disease-linked deubiquitinating enzyme regulates several of its cellular properties, which in turn may influence disease pathogenesis...
  69. ncbi SCA 1, SCA 2 & SCA 3/MJD mutations in ataxia syndromes in southern India
    Nithin Krishna
    Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India
    Indian J Med Res 126:465-70. 2007
    ..We carried out this study to assess the occurrence of SCA1, 2 and 3, at a tertiary neuro-psychiatric center in Bangalore, Karnataka...
  70. pmc Inhibition of p97-dependent protein degradation by Eeyarestatin I
    Qiuyan Wang
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:7445-54. 2008
    ..Interestingly, p97-associated deubiquitination is also involved in degradation of a soluble substrate. Our analyses establish a role for a novel deubiquitinating process in proteasome-dependent protein turnover...
  71. doi Study of subcellular localization and proteolysis of ataxin-3
    Chiara Pozzi
    Dipartimento di Biotecnologie e Bioscienze, Universita di Milano Bicocca, P za della Scienza 2, 20126 Milan, Italy
    Neurobiol Dis 30:190-200. 2008
    ..This may play a role in the pathogenesis, hampering degradation of aggregation-prone expanded AT-3. In addition, autolytic cleavage was apparently not involved in AT-3 proteolysis...
  72. doi Homozygosity enhances severity in spinocerebellar ataxia type 3
    Daniel R Carvalho
    Genetic Unit, Sarah Network of Rehabilitation Hospitals, Brasilia, DF, Brazil
    Pediatr Neurol 38:296-9. 2008
    ..All affected individuals have an expanded CAG repeat mutation in one allele of the ATXN3 gene...
  73. doi Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease
    Sandro Alves
    Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
    Hum Mol Genet 17:2071-83. 2008
    Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein...
  74. pmc Casein kinase 2 interacts with and phosphorylates ataxin-3
    Rui Song Tao
    Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
    Neurosci Bull 24:271-7. 2008
    ..dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear...
  75. pmc Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3
    Sokol V Todi
    Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
    EMBO J 28:372-82. 2009
    ..Ataxin-3 is the first reported DUB in which ubiquitination directly regulates catalytic activity. We propose a new function for protein ubiquitination in regulating the activity of certain DUBs and perhaps other enzymes...
  76. doi Evolutionary divergence of valosin-containing protein/cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins
    Giacomo Morreale
    Laboratory of Molecular Signalling, The Babraham Institute, Cambridge, UK
    FEBS J 276:1208-20. 2009
    ..degradation protein 2a (Ufd2a), hydroxymethylglutaryl reductase degradation protein 1 (Hrd1)-synoviolin and ataxin 3, and a related sequence in M(r) 78,000 glycoprotein-Amfr with slightly different binding properties, and show ..
  77. pmc Nucleocytoplasmic shuttling activity of ataxin-3
    Sandra Macedo-Ribeiro
    IBMC Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
    PLoS ONE 4:e5834. 2009
    ..Curiously, the N-terminal Josephin domain alone is exported into the cytoplasm, but the nuclear export activity of Atx3 is significantly enhanced in ..
  78. doi CK2-dependent phosphorylation determines cellular localization and stability of ataxin-3
    Thorsten Mueller
    Department of Neurology, Friedrich Wilhelms University Bonn, UKB, 53105 Bonn, Germany
    Hum Mol Genet 18:3334-43. 2009
    ..kinase 2 (CK2)-dependent phosphorylation controls the nuclear localization, aggregation and stability of ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3)...
  79. doi Identification and functional dissection of localization signals within ataxin-3
    Paul Michel Aloyse Antony
    Medical Genetics, University of Tubingen, Calwerstrasse 7, 72076 Tubingen, Germany
    Neurobiol Dis 36:280-92. 2009
    Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ..
  80. doi Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation
    Zheng Ying
    Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui, People s Republic of China
    Hum Mol Genet 18:4268-81. 2009
    ..Furthermore, gp78 is increased in cells transfected with these two mutant proteins as well as in ALS mice. Thus, our results suggest that gp78 functions in the regulation of SOD1 and ataxin-3 to target them for ERAD...
  81. doi Proteomic and biochemical analyses unveil tight interaction of ataxin-3 with tubulin
    Serena Mazzucchelli
    Dipartimento di Biotecnologie e Bioscienze, Universita di Milano Bicocca, Piazza della Scienza 2, I 20126 Milano, Italy
    Int J Biochem Cell Biol 41:2485-92. 2009
    Ataxin-3 consists of an N-terminal globular Josephin domain and an unstructured C-terminal region containing a stretch of consecutive glutamines that triggers an inherited neurodegenerative disorder, spinocerebellar ataxia type 3, when ..
  82. doi Increased transcript diversity: novel splicing variants of Machado-Joseph disease gene (ATXN3)
    Conceição Bettencourt
    Center of Research in Natural Resources CIRN, University of the Azores, Ponta Delgada, Portugal
    Neurogenetics 11:193-202. 2010
    ..MJD is caused by an expansion of a CAG tract at exon 10 of the ATXN3 gene (14q32.1), which encodes for ataxin-3...
  83. doi Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products
    Anabela Silva-Fernandes
    Life and Health Sciences Research Institute ICVS, School of Health Sciences, University of Minho, Campus de Gualtar, 4710 057 Braga, Portugal
    Neurobiol Dis 40:163-76. 2010
    Machado-Joseph disease (MJD) is a late-onset neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the ataxin-3 protein...
  84. doi Absence of ataxin-3 leads to cytoskeletal disorganization and increased cell death
    Ana João Rodrigues
    Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
    Biochim Biophys Acta 1803:1154-63. 2010
    Ataxin-3 (ATXN3) is a widely expressed protein that binds to ubiquitylated proteins, has deubiquitylating activity in vitro and is thought to modulate substrate degradation through the ubiquitin-proteasome pathway...
  85. pmc Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117
    Sokol V Todi
    Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 285:39303-13. 2010
    ....
  86. doi p53 activation mediates polyglutamine-expanded ataxin-3 upregulation of Bax expression in cerebellar and pontine nuclei neurons
    An Hsun Chou
    Department of Anesthesiology, Chang Gung Memorial Hospital, Kwei San, Tao Yuan, Taiwan, ROC
    Neurochem Int 58:145-52. 2011
    Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by polyglutamine-expanded ataxin-3. SCA3 neurodegeneration is found in the pontine nuclei and cerebellum...
  87. pmc Crystal structure of a Josephin-ubiquitin complex: evolutionary restraints on ataxin-3 deubiquitinating activity
    Stephen D Weeks
    Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA
    J Biol Chem 286:4555-65. 2011
    The Josephin domain is a conserved cysteine protease domain found in four human deubiquitinating enzymes: ataxin-3, the ataxin-3-like protein (ATXN3L), Josephin-1, and Josephin-2...
  88. doi Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain
    Yukio Takeshita
    Department of Neuroscience, Yamaguchi Graduate University School of Medicine, Ube, Yamaguchi, Japan
    Neuroreport 22:232-8. 2011
    ..The results clearly showed that HAP1/STB interacts with the normal ataxin-3 through Josephin domain and polyglutamine-expanded mutants derived from SCA3 as well...
  89. pmc Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein
    Helen M Saunders
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
    Protein Sci 20:1675-81. 2011
    ..Ataxin-3, the causative protein of SCA3, contains a globular, structured N-terminal domain (the Josephin domain) and a flexible polyQ-containing C-terminal tail, the repeat-length of which modulates pathogenicity...
  90. pmc Machado-Joseph disease/spinocerebellar ataxia type 3
    Henry Paulson
    Department of Neurology, University of Michigan, Ann Arbor, MI 48109 2200, USA
    Handb Clin Neurol 103:437-49. 2012
    Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), may be the most common dominantly inherited ataxia in the world...
  91. pmc Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP
    K Matthew Scaglione
    Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Cell 43:599-612. 2011
    ..In addition, the results shed light on disease pathogenesis in SCA3, a neurodegenerative disorder caused by polyglutamine expansion in ataxin-3.
  92. doi Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease
    Philipp Koch
    Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, 53127 Bonn, Germany
    Nature 480:543-6. 2011
    ..liberation of highly aggregation-prone polyQ fragments from the protective sequence of the MJD1 gene product ataxin 3 (ATXN3) has been proposed to trigger the formation of ATXN3-containing aggregates, the neuropathological hallmark ..
  93. doi Sequence analysis of 5' regulatory regions of the Machado-Joseph disease gene (ATXN3)
    Conceição Bettencourt
    Institute for Molecular and Cell Biology IBMC, University of Porto, Porto, Portugal
    Cerebellum 11:1045-50. 2012
    ..a late-onset autosomal dominant neurodegenerative disorder, which is caused by a coding (CAG)(n) expansion in the ATXN3 gene (14q32.1)...
  94. pmc Ataxin-3 regulates aggresome formation of copper-zinc superoxide dismutase (SOD1) by editing K63-linked polyubiquitin chains
    Hongfeng Wang
    Laboratory of Molecular Neuropathology, Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, Suzhou, Jiangsu 215123, China
    J Biol Chem 287:28576-85. 2012
    ..Thus, our data suggest that the sequestration of misfolded SOD1 into aggresomes, which is driven by ataxin-3, plays an important role in attenuating protein misfolding-induced cell toxicity...
  95. doi Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease
    Ana T Simões
    Centre for Neuroscience and Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal Faculty of Pharmacy, University of Coimbra, 3000 548 Coimbra, Portugal
    Brain 135:2428-39. 2012
    ..Over-repetition of a CAG trinucleotide in the MJD1 gene translates into a polyglutamine tract within the ataxin 3 protein, which upon proteolysis may trigger Machado-Joseph disease...
  96. pmc Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice
    Clévio Nóbrega
    CNC Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
    PLoS ONE 8:e52396. 2013
    ..is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene...
  97. doi Ataxin-3 protects cells against H2O2-induced oxidative stress by enhancing the interaction between Bcl-X(L) and Bax
    L Zhou
    Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China
    Neuroscience 243:14-21. 2013
    Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder associated with polyglutamine (polyQ) protein ataxin-3...
  98. pmc JosD1, a membrane-targeted deubiquitinating enzyme, is activated by ubiquitination and regulates membrane dynamics, cell motility, and endocytosis
    Takahiro Seki
    Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 288:17145-55. 2013
    ..The MJD family of DUBs consists of four cysteine proteases that share a catalytic "Josephin" domain...
  99. pmc Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo
    Wei Ling Tsou
    From the Departments of Pharmacology and Neurology and
    J Biol Chem 288:34460-9. 2013
    ..Our work also suggests that ataxin-3 suppresses degeneration by regulating toxic protein aggregation rather than stability. ..
  100. ncbi Characterization of the structure and the amyloidogenic properties of the Josephin domain of the polyglutamine-containing protein ataxin-3
    Laura Masino
    National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
    J Mol Biol 344:1021-35. 2004
    ..study, we determined the domain architecture of ataxin-3, suggesting that it comprises a globular domain, named Josephin, and a more flexible C-terminal region, that includes the polyQ tract...
  101. ncbi Evaluation of the effect of sulphametoxazole and trimethoprim in patients with Machado-Joseph disease
    M Correia
    Neurology Department, , Porto, Portugal
    Rev Neurol 23:632-4. 1995
    The treatment of Machado-Joseph disease (MJD) has so far been purely symptomatic...

Research Grants60

  1. Triplet Repeat Disease:Requirement for Caspase Cleavage
    Lisa Ellerby; Fiscal Year: 2007
    ..disease (HD), spinal and bulbar muscular atrophy (SBMA, Kennedy's disease), Machado-Joseph disease (MJD or SCA-3), dentatorubropallidoluysian atrophy (DRPLA), and spinocerebellar ataxias types 1, 2, and 6 (SCA-1, SCA-2, ..
  2. MECHANISMS OF POLYGLUTAMINE NEUROTOXICITY
    William Herring; Fiscal Year: 1999
    ..is a progressive neurodegenerative disorder found to result from CAG trinucleotide repeat expansion within the MJD1 gene on human chromosome 14q32.1...
  3. Tapas K Hazra; Fiscal Year: 2016
    ..Our surprising observation of the association of PNKP with Ataxin-3 (ATXN3), a protein responsible for spinocerebellar ataxia type 3, also called Machado-Joseph Disease (MJD/SCA3), prompted ..
  4. Structures and functions of the human Josephin domain-containing proteins
    Patrick J Loll; Fiscal Year: 2012
    The Josephin domain-containing proteins are one of the five major families of deubiquitinating enzymes (DUBs)...
  5. GULIN OZ; Fiscal Year: 2014
    ..Aim # 2) To identify the 1H MRS biomarkers that reflect disease severity in patients with SCA2, SCA3 and SCA6 and to determine if MRS biomarkers are disease specific by a cross- sectional comparison of neurochemical ..
  6. Dietary Factors Affecting Calcium and Zinc Absorption
    Steven Abrams; Fiscal Year: 2006
    ..age 2-8 yrs with clinical and biochemical evidence of rickets and 18 age- and gender-matched healthy, children in Jos, Nigeria...
  7. Norma C Ware; Fiscal Year: 2014
    ..The program will take place at Harvard University, Cambridge, MA, USA;Jos University, Jos, Nigeria;and Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania...
  8. DAVID OLUFEMI OLALEYE; Fiscal Year: 2015
    ..The University of Ibadan is the lead medical school with partners including: University of Jos, University of Nigeria, University of Maiduguri, Ahmadu Bello University, University of Lagos, the AIDS Prevention ..
  9. Northwestern University AITRP
    Robert L Murphy; Fiscal Year: 2012
    ..between the faculty at NU and the faculty at University College Hospital (UCH)AJniversity of Ibadan in Ibadan and Jos University Teaching Hospital (JUTH) in Jos, Nigeria...
  10. Emmanuel Idigbe; Fiscal Year: 2015
    ..utilize data and samples from patients that have received ART at the Nigerian Institute of Medical Research (NIMR), Jos University Teaching Hospital (JUTH), and University College Hospital in Ibadan (UCH) in Nigeria...
  11. Carrie M Nielson; Fiscal Year: 2016
    ..The plan has oversight by my primary mentor, Dr. Eric Orwoll, and my co- mentors, Drs. Robert Klein, Jos[unreadable] Luis Mill[unreadable]n and Bruce Weir...
  12. VIKRAM GOVINDARAJU SHAKKOTTAI; Fiscal Year: 2014
    ..My preliminary studies in a mouse model of the polyglutamine disorder Spinocerebellar Ataxia Type 3 (SCA3) have identified altered firing properties of one class of pacemaker neurons, the cerebellar Purkinje neurons, and ..
  13. Phosphatidylinositol Signaling and Human Disease
    Philip W Majerus; Fiscal Year: 2010
    ..The enzyme is inositol polyphosphate 5-phosphataseIV a lipid specific 5-PtaseIV. Dr Jos Gleeson (UCSD/HHMI) has found 5 different mutations in families with Joubert syndrome and has sent us cells and ..
  14. Ronald R Hoy; Fiscal Year: 2014
    ..They possess antennae attached to Johnston's hearing organs (JOs) as external appendages on their heads...
  15. Effect of apoE on CNS neurons: Role of LRP
    David M Holtzman; Fiscal Year: 2013
    ..Determining the effects of altering the levels of different apoE isoforms on At3 in vivo as well as the mechanism(s) underlying these effects is likely to lead to importanl insights into AD and ..
  16. Jerry L Prince; Fiscal Year: 2015
    ..Specific hypotheses related to patterns of degeneration and corresponding functional deficits in SCA2, SCA3, and SCA6 will be tested, and a preliminary map of the topography of functional scores on a low- dimensional shape ..
  17. TUMAINI RUCKER COKER; Fiscal Year: 2014
    ..b>Jos[unreadable] J. Escarce. At the end of the proposed career development period, Dr...
  18. Biswarathan Ramani; Fiscal Year: 2015
    ..fatal, and untreatable neurodegenerative disorder caused by a polyglutamine-encoding CAG expansion in the ATXN3 gene...
  19. ILYA B BEZPROZVANNY; Fiscal Year: 2016
    ..propose to apply similar ideas to understanding the mechanisms of pathogenesis in spinocerebellar ataxia type 3 (SCA3), another member of polyQ-expansion disorders family. Specifically, I propose: 1...
  20. Toxic intermediates and protein quality control in SCA3
    AISLINN J WILLIAMS; Fiscal Year: 2010
    ..Spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited ataxia, is caused by an expansion of a glutamine repeat in the C-terminus of ..
  21. Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors
    MARIANO A GARCIABLANCO; Fiscal Year: 2013
    ..To visualize the use of FGFR2 exon IIIc in Dunning AT3 tumors in syngeneic rats we constructed minigene constructs that report on alternative splicing...
  22. Development of a Knock-in Mouse Model for Spinocerebellar Ataxia Type 3
    Henry L Paulson; Fiscal Year: 2012
    ..The current studies will build on our recent success targeting a human CAG repeat expansion into the murine Atxn3 locus, resulting in mice that express polyQ-expanded (pathogenic) ataxin-3...
  23. Modeling Huntington's Disease in Drosophila
    J Littleton; Fiscal Year: 2009
    ..an expanded polyglutamine tract alone, or an expanded polyglutamine tract in the context of the spinocerebellar ataxia type 3 protein, display only nuclear aggregates and do not disrupt axonal trafficking...
  24. 2013 Staphylococcal Diseases Gordon Research Conference and Gordon Research Semin
    Vance G Fowler; Fiscal Year: 2013
    ..As is the conference custom, they will now serve as Co- Chairs of the 2013 meeting, with Drs. Simon Foster and Jos van Stripj serving as Co-Vice Chairs. Drs. Michael Olson and Karen Beenken will serve as Co-Chairs of the GRS...
  25. Henry L Paulson; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The most common dominantly inherited ataxia, Spinocerebellar Ataxia Type 3 (SCA3) is also one of nine neurodegenerative diseases caused by polyglutamine expansion...
  26. HTS to Identify Small Molecules Targeting Repeating Transcripts
    Matthew D Disney; Fiscal Year: 2013
    ..present in the expanded r(CAG) repeats that cause Huntington's Disease (HD) and Spinocerebellar Ataxia Type 3 (SCA3), which have no known cures...
  27. SIGNALS OF OXIDANT INDUCED CARDIOMYOCYTE HYPERTROPHY
    Qin Chen; Fiscal Year: 1999
    ..involves elevated expression of a number of genes, activation of MAP kinases and calcium mediated activation of NF-AT3. Since H2O2 has been reported to activate MAP kinases and increase cytosolic calcium, we hypothesize that H2O2 ..
  28. JULIA B DICKSON-GOMEZ; Fiscal Year: 2015
    ..research collaboration between the Center for AIDS Intervention Research (CAIR), the Universidad Centroamericana Jos[unreadable] Sime[unreadable]n Ca[unreadable]as (UCA) and the Fundaci[unreadable]n Antidrogas de El Salvador (..
  29. CLEBER COSTA OUVERNEY; Fiscal Year: 2016
    ..and research training in biomedically-related fields for underrepresented, honors undergraduates at San Jos[unreadable] State University (SJSU). In so doing, we will increase the number of SJSU students entering Ph.D...
  30. SPECT Imaging of Abeta Plaques in Brain
    Mei Ping Kung; Fiscal Year: 2006
    ..tracers for binding A13 plaques suggest that there are specific and saturable binding sites on the aggregates of At3 that can be selectively labeled and imaged in vivo...
  31. NF-AT3 IN CARDIOVASCULAR BIOLOGY
    EUGENE KAJI; Fiscal Year: 2004
    ..Previously, others have implicated the serine phosphatase calcineurin and the transcription factor NF-AT3 as central mediators of cardiac hypertrophy...
  32. PATHOGENESIS STUDIES OF SPINOCEREBELLAR ATAXIA TYPE 6
    Cheng Lee; Fiscal Year: 2001
    ..Compared to other known polyglutamine diseases like SCA 1, SCA2, SCA3, SMBA, DRPLA and HD, the expanded mutant alleles in SCA6 (21-27 repeats) are remarkably smaller than the expanded ..
  33. DESENSITIZATION OF LH SECRETION BY GNRH
    JIMMY NEILL; Fiscal Year: 1999
    ..us to inhibit GnRH-stimulated cellular inositol trisphosphate (IP3) levels, its mRNA is present in the gonadotropic aT3-1 cell line, and RGS is detected by antibodies in membranes of aT3-1 and pituitary cells...
  34. Small animal module for translational MR neuroimaging at3 Tesla
    Kamel Khalili; Fiscal Year: 2009
    ..In vivo imaging of these models will allow us to test and validate non-invasive novel diagnostic and therapeutic strategies that can be directly used in the clinic. ..
  35. Mouse Model and Interactors for Machado-Joseph Disease
    Veronica Colomer; Fiscal Year: 2004
    DESCRIPTION (Adapted from applicant's abstract): Machado Joseph disease (MJD), or spinocerebellar ataxia-3 (SCA-3), is the most common dominant spinocerebellar ataxia...
  36. IDENTIFYING NIDDM GENES USING ADMIXED POPULATIONS
    Mark Shriver; Fiscal Year: 2001
    ..They will verify any positive associations found using sib-pair linkage analysis and the transmission disequilibrium test. ..
  37. Presenilins and neuronal calcium signaling
    ILYA B BEZPROZVANNY; Fiscal Year: 2010
    ..These data will also help to evaluate "Ca2+ hypothesis of AD" and will contribute to selecting optimal strategies for treatment of AD. ..
  38. Identification of targets of FoxP2 in the brain
    Daniel Geschwind; Fiscal Year: 2006
    ..This proposal has a strong screening component in an area where no molecular mechanisms have been identified and fits well within the R21 framework. ..
  39. Social Course of Adherence to HAART in Active Drug Users
    Norma Ware; Fiscal Year: 2003
    ..These categories will serve as the basis for formulating and assessing the feasibility of patient focused, clinician-focused, and other strategies for supporting adherence to HAART among active users of illegal drugs. ..
  40. MOLECULAR GENETICS OF THE SCA1 LOCUS
    Harry Orr; Fiscal Year: 2003
    ..Understanding the importance of these factors for SCA1 pathogenesis should provide insights for polyglutamine diseases in general. ..
  41. INTERACTIONS OF CALCIUM CHANNELS WITH ADAPTOR PROTEINS
    Ilya Bezprozvanny; Fiscal Year: 2003
    ....
  42. THE GENETICS OF IDIOPATHIC BASAL GANGLIA CALCIFICATION
    Daniel Geschwind; Fiscal Year: 2004
    ..Physical mapping and candidate screening for mutations will be pursued as the region is narrowed to identify the IBGC gene. A genome scan will be performed in families who are not linked to the chr.14 locus. ..
  43. Social Integration for Psychiatrically Disabled Adults
    Norma Ware; Fiscal Year: 2005
    ..abstract_text> ..
  44. Screen:Blockers of a CaV2.2-Mint-PDZ1 association (RMI)
    Ilya Bezprozvanny; Fiscal Year: 2004
    ..Biological activity of compounds identified in the full HTS screen will be tested in whole animal pain assays (formalin, hot plate, tail flick). ..
  45. A Genomewide Search for Autism Susceptibilty Loci
    Daniel Geschwind; Fiscal Year: 2006
    ..All phenotypic and genotype data will be made accessible via the Internet on a rolling basis, further enhancing the value of this resource to the community. ..
  46. ASYMMETRICALLY EXPRESSED GENES IN DEVELOPING CEREBRUM
    Daniel Geschwind; Fiscal Year: 2003
    ..abstract_text> ..
  47. CONSTRUCTION AND APPLICATION OF A US ADMIXTURE MAP
    Mark Shriver; Fiscal Year: 2006
    ..From simulation studies, we estimate that about 1000 AIMs will be required for genome-wide mapping with two-way admixture, and about 1500 for admixture between three populations. [unreadable] [unreadable] [unreadable]..
  48. Regulation of the SCA3 Disease Gene and Its Protein
    SARAH BERKE; Fiscal Year: 2003
    ..pathways controlling ataxin-3 degradation, and to define the transcriptional regulation of the SCA3 disease gene, MJD1. Specifically, studies in aim 1 hope to demonstrate that ataxin-3 is a normal target for proteasome and caspase ..
  49. Analysis of Fbx2 Family of Ubiquitin Ligases
    Henry Paulson; Fiscal Year: 2007
    ..The results may also have implications for the pathogenesis of two poorly understood neurological diseases, DYT1 dystonia and familial neuroserpin dementia. ..
  50. Influences on Adherence to ARVs in Uganda
    Norma Ware; Fiscal Year: 2007
    ..Practical intervention strategies will be derived as the basis for intervention design and testing, which follow as next steps from this research. [unreadable] [unreadable] [unreadable]..
  51. MOLECULAR GENETIC CHARACTERIZATION OF SCA7
    Harry Orr; Fiscal Year: 2002
    ..To gain insight into ataxin-7 function a series of experiments are proposed to characterize the cellular and subcellular expression of ataxin-7 and to identify proteins that interact with ataxin-7 using the yeast two-hybrid system. ..
  52. Metabolomics and metabolic compartmentation in the brain
    Julian Griffin; Fiscal Year: 2006
    ..To correlate NMR observable metabolite changes with transcriptional changes. Our data will provide proof-of principle for this methodology, and establish a means for exploring other neurolodegenerative disorders. ..
  53. 2008 Calcium Signaling and Disease SGP Conference
    Ilya Bezprozvanny; Fiscal Year: 2008
    ..The major purpose of the SGP is to host a symposium each year on a different subject of wide interest to cell biologists, physiologists and biophysicists. [unreadable] [unreadable] [unreadable]..
  54. HTS Screen for Small Molecule Inhibitors of Mint-PDZ Domain
    Ilya Bezprozvanny; Fiscal Year: 2008
    ..Generated molecules may also serve as useful probes for studies of synaptic function of N-type Ca2+ channels. [unreadable] [unreadable] [unreadable]..
  55. Structure-function of inositol trisphosphate receptor
    Ilya Bezprozvanny; Fiscal Year: 2009
    ..Dopamine-induced responses in striatal medium spiny neurons will be studied by Ca2+ imaging. Experiments with striatal neurons from DARPP-32 and D2 receptor knockout mice will be performed. ..
  56. Novel Genetic Risk Factors for Alzheimer's Disease (AD) & Frontotemporal Dementia
    Daniel Geschwind; Fiscal Year: 2009
    ..abstract_text> ..