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
Products:     ATXN3

Top Publications

  1. Chai Y, Shao J, Miller V, Williams A, Paulson H. Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis. Proc Natl Acad Sci U S A. 2002;99:9310-5 pubmed
  2. Marchal S, Shehi E, Harricane M, Fusi P, Heitz F, Tortora P, et al. Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature. J Biol Chem. 2003;278:31554-63 pubmed
    ..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. ..
  3. Wu Y, Lin H, Chen C, Gwinn Hardy K, Ro L, Wang Y, et al. Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease. Clin Genet. 2004;65:209-14 pubmed
    ..MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%)...
  4. Goti D, Katzen S, Mez J, Kurtis N, Kiluk J, Ben Haïem L, et al. A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration. J Neurosci. 2004;24:10266-79 pubmed
    Machado-Joseph disease (MJD) is an inherited neurodegenerative disorder caused by ataxin-3 with a polyglutamine expansion...
  5. Colomer Gould V, Goti D, Pearce D, Gonzalez G, Gao H, Bermudez de Leon M, et al. 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. Neurobiol Dis. 2007;27:362-9 pubmed
    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)...
  6. Evert B, Araujo J, Vieira Saecker A, de Vos R, Harendza S, Klockgether T, et al. Ataxin-3 represses transcription via chromatin binding, interaction with histone deacetylase 3, and histone deacetylation. J Neurosci. 2006;26:11474-86 pubmed
    Ataxin-3 (AT3), the disease protein in spinocerebellar ataxia type 3 (SCA3), has been associated with the ubiquitin-proteasome system and transcriptional regulation...
  7. Ichikawa Y, Goto J, Hattori M, Toyoda A, Ishii K, Jeong S, et al. The genomic structure and expression of MJD, the Machado-Joseph disease gene. J Hum Genet. 2001;46:413-22 pubmed
    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder that is clinically characterized by cerebellar ataxia and various associated symptoms...
  8. Matsumoto M, Yada M, Hatakeyama S, Ishimoto H, Tanimura T, Tsuji S, et al. Molecular clearance of ataxin-3 is regulated by a mammalian E4. EMBO J. 2004;23:659-69 pubmed
    ..in which the abnormal expansion of a polyglutamine tract is responsible for spinocerebellar ataxia type 3 (SCA3), undergoes ubiquitylation and degradation by the proteasome...
  9. Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, et al. The gene for Machado-Joseph disease maps to human chromosome 14q. Nat Genet. 1993;4:300-4 pubmed
    Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems...

More Information

Publications83

  1. Li L, Yu Z, Teng X, Bonini N. RNA toxicity is a component of ataxin-3 degeneration in Drosophila. Nature. 2008;453:1107-11 pubmed publisher
    ..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 ..
  2. Harris G, Dodelzon K, Gong L, Gonzalez Alegre P, Paulson H. Splice isoforms of the polyglutamine disease protein ataxin-3 exhibit similar enzymatic yet different aggregation properties. PLoS ONE. 2010;5:e13695 pubmed publisher
    ..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 (..
  3. Bichelmeier U, Schmidt T, Hübener J, Boy J, Ruttiger L, Häbig K, et al. Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence. J Neurosci. 2007;27:7418-28 pubmed
    ..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...
  4. Wang H, Jia N, Fei E, Wang Z, Liu C, Zhang T, et al. p45, an ATPase subunit of the 19S proteasome, targets the polyglutamine disease protein ataxin-3 to the proteasome. J Neurochem. 2007;101:1651-61 pubmed
    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...
  5. Ferro A, Carvalho A, Teixeira Castro A, Almeida C, Tomé R, Cortes L, et al. NEDD8: a new ataxin-3 interactor. Biochim Biophys Acta. 2007;1773:1619-27 pubmed
    ..that this interaction is not dependent on the ubiquitin-interacting motifs in ataxin-3, since the presence of the Josephin domain is sufficient for the interaction to occur...
  6. Wang Q, Li L, Ye Y. Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3. J Cell Biol. 2006;174:963-71 pubmed
    ..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...
  7. Tait D, Riccio M, Sittler A, Scherzinger E, Santi S, Ognibene A, et al. Ataxin-3 is transported into the nucleus and associates with the nuclear matrix. Hum Mol Genet. 1998;7:991-7 pubmed
    ..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. ..
  8. Macedo Ribeiro S, Cortes L, Maciel P, Carvalho A. Nucleocytoplasmic shuttling activity of ataxin-3. PLoS ONE. 2009;4:e5834 pubmed publisher
    ..Curiously, the N-terminal Josephin domain alone is exported into the cytoplasm, but the nuclear export activity of Atx3 is significantly enhanced in ..
  9. Paulson H, Das S, Crino P, Perez M, Patel S, Gotsdiner D, et al. Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain. Ann Neurol. 1997;41:453-62 pubmed
    ..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...
  10. Rodrigues A, do Carmo Costa M, Silva T, Ferreira D, Bajanca F, Logarinho E, et al. Absence of ataxin-3 leads to cytoskeletal disorganization and increased cell death. Biochim Biophys Acta. 2010;1803:1154-63 pubmed publisher
    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...
  11. Saunders H, Gilis D, Rooman M, Dehouck Y, Robertson A, Bottomley S. Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein. Protein Sci. 2011;20:1675-81 pubmed publisher
    ..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...
  12. Mao Y, Senic Matuglia F, Di Fiore P, Polo S, Hodsdon M, De Camilli P. Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain. Proc Natl Acad Sci U S A. 2005;102:12700-5 pubmed
    ..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 ..
  13. Reina C, Zhong X, Pittman R. Proteotoxic stress increases nuclear localization of ataxin-3. Hum Mol Genet. 2010;19:235-49 pubmed publisher
    ..Mapping studies showed that two regions of Atx3, the Josephin domain and the C-terminus, regulated heat shock-induced nuclear localization...
  14. Tao R, Fei E, Ying Z, Wang H, Wang G. Casein kinase 2 interacts with and phosphorylates ataxin-3. Neurosci Bull. 2008;24:271-7 pubmed publisher
    Machado-Joseph disease (MJD)/Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3...
  15. Mazzucchelli S, De Palma A, Riva M, D Urzo A, Pozzi C, Pastori V, et al. Proteomic and biochemical analyses unveil tight interaction of ataxin-3 with tubulin. Int J Biochem Cell Biol. 2009;41:2485-92 pubmed publisher
    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 ..
  16. Pozzi C, Valtorta M, Tedeschi G, Galbusera E, Pastori V, Bigi A, et al. Study of subcellular localization and proteolysis of ataxin-3. Neurobiol Dis. 2008;30:190-200 pubmed publisher
    ..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...
  17. Jung J, Xu K, Lessing D, Bonini N. Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3. Hum Mol Genet. 2009;18:4843-52 pubmed publisher
    ..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 ..
  18. Weeks S, Grasty K, Hernandez Cuebas L, Loll P. Crystal structure of a Josephin-ubiquitin complex: evolutionary restraints on ataxin-3 deubiquitinating activity. J Biol Chem. 2011;286:4555-65 pubmed publisher
    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...
  19. Chai Y, Berke S, Cohen R, Paulson H. Poly-ubiquitin binding by the polyglutamine disease protein ataxin-3 links its normal function to protein surveillance pathways. J Biol Chem. 2004;279:3605-11 pubmed
    ..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...
  20. Durcan T, Kontogiannea M, Bedard N, Wing S, Fon E. Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme. J Biol Chem. 2012;287:531-41 pubmed publisher
  21. Haacke A, Hartl F, Breuer P. Calpain inhibition is sufficient to suppress aggregation of polyglutamine-expanded ataxin-3. J Biol Chem. 2007;282:18851-6 pubmed
    ..These findings suggest a critical role of calpains in the pathogenesis of Spinocerebellar ataxia type 3...
  22. Silva Fernandes A, Costa M, Duarte Silva S, Oliveira P, Botelho C, Martins L, et al. Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiol Dis. 2010;40:163-76 pubmed publisher
    Machado-Joseph disease (MJD) is a late-onset neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the ataxin-3 protein...
  23. Todi S, Scaglione K, Blount J, Basrur V, Conlon K, Pastore A, et al. Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117. J Biol Chem. 2010;285:39303-13 pubmed publisher
  24. Takeshita Y, Fujinaga R, Kokubu K, Islam M, Jahan M, Yanai A, et al. Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain. Neuroreport. 2011;22:232-8 pubmed publisher
    ..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...
  25. Nicastro G, Todi S, Karaca E, Bonvin A, Paulson H, Pastore A. Understanding the role of the Josephin domain in the PolyUb binding and cleavage properties of ataxin-3. PLoS ONE. 2010;5:e12430 pubmed publisher
    ..which it anchors polyubiquitin chains of different linkages that are then cleaved by the N-terminal catalytic (Josephin) domain...
  26. Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A. Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat Genet. 1996;13:196-202 pubmed
    Recently, we identified a novel gene, MJD1, which contains an expanded CAG triplet repeat in Machado-Joseph disease...
  27. Apicella A, Natalello A, Frana A, Baserga A, Casari C, Bottani C, et al. Temperature profoundly affects ataxin-3 fibrillogenesis. Biochimie. 2012;94:1026-31 pubmed publisher
    Ataxin-3 (AT3) triggers spinocerebellar ataxia type 3 when it carries a polyglutamine stretch expanded beyond a critical threshold...
  28. Zhong X, Pittman R. Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates. Hum Mol Genet. 2006;15:2409-20 pubmed
    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...
  29. Shen L, Tang J, Tang B, Jiang H, Zhao G, Xia K, et al. Research on screening and identification of proteins interacting with ataxin-3. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005;22:242-7 pubmed
    ..the function of ataxin-3 and the pathogenesis of spinocerebellar ataxia type 3 and Machado-Joseph disease (SCA3/MJD)...
  30. Krishna N, Mohan S, Yashavantha B, Rammurthy A, Kiran Kumar H, Mittal U, et al. SCA 1, SCA 2 & SCA 3/MJD mutations in ataxia syndromes in southern India. Indian J Med Res. 2007;126:465-70 pubmed
    ..with established family history and autosomal dominant inheritance SCA1 was most prevalent followed by SCA2 and SCA3. Our findings suggested SCA1 rather than SCA2 to be the more common mutation in southern India...
  31. Alves S, Regulier E, Nascimento Ferreira I, Hassig R, Dufour N, Koeppen A, et al. Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease. Hum Mol Genet. 2008;17:2071-83 pubmed publisher
    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...
  32. Masino L, Nicastro G, Menon R, Dal Piaz F, Calder L, Pastore A. Characterization of the structure and the amyloidogenic properties of the Josephin domain of the polyglutamine-containing protein ataxin-3. J Mol Biol. 2004;344:1021-35 pubmed
    ..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...
  33. Wang Q, Li L, Ye Y. Inhibition of p97-dependent protein degradation by Eeyarestatin I. J Biol Chem. 2008;283:7445-54 pubmed publisher
    ..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. ..
  34. Scaglione K, Zavodszky E, Todi S, Patury S, Xu P, Rodriguez Lebron E, et al. Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Mol Cell. 2011;43:599-612 pubmed publisher
    ..In addition, the results shed light on disease pathogenesis in SCA3, a neurodegenerative disorder caused by polyglutamine expansion in ataxin-3.
  35. Albrecht M, Golatta M, Wullner U, Lengauer T. Structural and functional analysis of ataxin-2 and ataxin-3. Eur J Biochem. 2004;271:3155-70 pubmed
    ..the construction of tertiary structure models of the RNA-binding Lsm domain of ataxin-2 and the deubiquitinating Josephin domain of ataxin-3...
  36. Masino L, Musi V, Menon R, Fusi P, Kelly G, Frenkiel T, et al. Domain architecture of the polyglutamine protein ataxin-3: a globular domain followed by a flexible tail. FEBS Lett. 2003;549:21-5 pubmed
    ..Moreover, [(15)N]glutamine selectively labelled samples allowed us to have a direct insight by NMR into the structure of the polyQ region. ..
  37. Nicastro G, Masino L, Esposito V, Menon R, De Simone A, Fraternali F, et al. Josephin domain of ataxin-3 contains two distinct ubiquitin-binding sites. Biopolymers. 2009;91:1203-14 pubmed publisher
    ..The enzymatic site resides in the N-terminal josephin domain of ataxin-3...
  38. Antony P, Mäntele S, Mollenkopf P, Boy J, Kehlenbach R, Riess O, et al. Identification and functional dissection of localization signals within ataxin-3. Neurobiol Dis. 2009;36:280-92 pubmed publisher
    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 ..
  39. Ying Z, Wang H, Fan H, Zhu X, Zhou J, Fei E, et al. Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Hum Mol Genet. 2009;18:4268-81 pubmed publisher
    ..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. ..
  40. Todi S, Laco M, Winborn B, Travis S, Wen H, Paulson H. Cellular turnover of the polyglutamine disease protein ataxin-3 is regulated by its catalytic activity. J Biol Chem. 2007;282:29348-58 pubmed
    ..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. ..
  41. Burnett B, Li F, Pittman R. The polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity. Hum Mol Genet. 2003;12:3195-205 pubmed
    ..Data in the present study suggest that the polyglutamine neurodegenerative disease protein, ataxin-3 (AT3), functions in the ubiquitin-proteasome pathway...
  42. Li L, Xu K, Bonini N. Suppression of polyglutamine toxicity by the yeast Sup35 prion domain in Drosophila. J Biol Chem. 2007;282:37694-701 pubmed
    ..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...
  43. Warrick J, Morabito L, Bilen J, Gordesky Gold B, Faust L, Paulson H, et al. Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism. Mol Cell. 2005;18:37-48 pubmed
    ..function and disease pathogenesis to ubiquitin pathways in the polyglutamine disease spinocerebellar ataxia type 3 (SCA3)...
  44. Masino L, Nicastro G, Calder L, Vendruscolo M, Pastore A. Functional interactions as a survival strategy against abnormal aggregation. FASEB J. 2011;25:45-54 pubmed publisher
    ..solubility and aggregation rates of ataxin-3, but these properties are profoundly modulated by its N-terminal Josephin domain...
  45. Boeddrich A, Gaumer S, Haacke A, Tzvetkov N, Albrecht M, Evert B, et al. An arginine/lysine-rich motif is crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis. EMBO J. 2006;25:1547-58 pubmed
    ..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. ..
  46. Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N. Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B. Hum Mol Genet. 2000;9:1795-803 pubmed
    ..dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3...
  47. Berke S, Schmied F, Brunt E, Ellerby L, Paulson H. Caspase-mediated proteolysis of the polyglutamine disease protein ataxin-3. J Neurochem. 2004;89:908-18 pubmed
    ..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...
  48. Zhou L, Wang H, Wang P, Ren H, Chen D, Ying Z, et al. Ataxin-3 protects cells against H2O2-induced oxidative stress by enhancing the interaction between Bcl-X(L) and Bax. Neuroscience. 2013;243:14-21 pubmed publisher
    Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder associated with polyglutamine (polyQ) protein ataxin-3...
  49. Morreale G, Conforti L, Coadwell J, Wilbrey A, Coleman M. Evolutionary divergence of valosin-containing protein/cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins. FEBS J. 2009;276:1208-20 pubmed publisher
    ..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 ..
  50. Winborn B, Travis S, Todi S, Scaglione K, Xu P, WILLIAMS A, et al. The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains. J Biol Chem. 2008;283:26436-43 pubmed publisher
    ..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 ..
  51. Durcan T, Kontogiannea M, Thorarinsdottir T, Fallon L, WILLIAMS A, Djarmati A, et al. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum Mol Genet. 2011;20:141-54 pubmed publisher
    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...
  52. Costa M, Sequeiros J, Maciel P. Identification of three novel polymorphisms in the MJD1 gene and study of their frequency in the Portuguese population. J Hum Genet. 2002;47:205-7 pubmed
    ..is an autosomal dominant neurodegenerative disorder of late onset, caused by the expansion of a (CAG)n tract in the MJD1 gene...
  53. Li F, Macfarlan T, Pittman R, Chakravarti D. Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities. J Biol Chem. 2002;277:45004-12 pubmed
  54. Ellisdon A, Thomas B, Bottomley S. The two-stage pathway of ataxin-3 fibrillogenesis involves a polyglutamine-independent step. J Biol Chem. 2006;281:16888-96 pubmed
    ..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-..
  55. Doss Pepe E, Stenroos E, Johnson W, Madura K. 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. Mol Cell Biol. 2003;23:6469-83 pubmed
  56. Burnett B, Pittman R. The polyglutamine neurodegenerative protein ataxin 3 regulates aggresome formation. Proc Natl Acad Sci U S A. 2005;102:4330-5 pubmed
    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...
  57. Chow M, Paulson H, Bottomley S. Destabilization of a non-pathological variant of ataxin-3 results in fibrillogenesis via a partially folded intermediate: a model for misfolding in polyglutamine disease. J Mol Biol. 2004;335:333-41 pubmed
    ..The implications of this are considered in the wider context of the development and pathogenesis of polyglutamine diseases. ..
  58. Simões A, Gonçalves N, Koeppen A, Déglon N, Kügler S, Duarte C, et al. Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease. Brain. 2012;135:2428-39 pubmed publisher
    ..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...
  59. Berke S, Chai Y, Marrs G, Wen H, Paulson H. Defining the role of ubiquitin-interacting motifs in the polyglutamine disease protein, ataxin-3. J Biol Chem. 2005;280:32026-34 pubmed
  60. Schols L, Vieira Saecker A, Schols S, Przuntek H, Epplen J, Riess O. Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients. Hum Mol Genet. 1995;4:1001-5 pubmed
    ..The MJD1 gene has recently been cloned and the disease causing mutation has been identified as an unstable and expanded (CAG)..
  61. Nóbrega C, Nascimento Ferreira I, Onofre I, Albuquerque D, Hirai H, Déglon N, et al. Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice. PLoS ONE. 2013;8:e52396 pubmed publisher
    ..is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene...
  62. Mueller T, Breuer P, Schmitt I, Walter J, Evert B, Wullner U. CK2-dependent phosphorylation determines cellular localization and stability of ataxin-3. Hum Mol Genet. 2009;18:3334-43 pubmed publisher
    ..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)...
  63. Gales L, Cortes L, Almeida C, Melo C, Costa M, Maciel P, et al. Towards a structural understanding of the fibrillization pathway in Machado-Joseph's disease: trapping early oligomers of non-expanded ataxin-3. J Mol Biol. 2005;353:642-54 pubmed
    ..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...
  64. Goto J, Watanabe M, Ichikawa Y, Yee S, Ihara N, Endo K, et al. Machado-Joseph disease gene products carrying different carboxyl termini. Neurosci Res. 1997;28:373-7 pubmed
    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...
  65. Paulson H. Machado-Joseph disease/spinocerebellar ataxia type 3. Handb Clin Neurol. 2012;103:437-49 pubmed publisher
    Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), may be the most common dominantly inherited ataxia in the world...
  66. Chen L, Madura K. Evidence for distinct functions for human DNA repair factors hHR23A and hHR23B. FEBS Lett. 2006;580:3401-8 pubmed
    ..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. ..
  67. Donaldson K, Li W, Ching K, Batalov S, Tsai C, Joazeiro C. Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc Natl Acad Sci U S A. 2003;100:8892-7 pubmed
    ..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. ..
  68. Shehi E, Fusi P, Secundo F, Pozzuolo S, Bairati A, Tortora P. Temperature-dependent, irreversible formation of amyloid fibrils by a soluble human ataxin-3 carrying a moderately expanded polyglutamine stretch (Q36). Biochemistry. 2003;42:14626-32 pubmed
    ..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. ..
  69. Chou A, Lin A, Hong K, Hu S, Chen Y, Chen J, et al. p53 activation mediates polyglutamine-expanded ataxin-3 upregulation of Bax expression in cerebellar and pontine nuclei neurons. Neurochem Int. 2011;58:145-52 pubmed publisher
    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...
  70. Alluri R, Komandur S, Wagheray A, Chaudhuri J, Sitajayalakshmi -, Meena A, et al. Molecular analysis of CAG repeats at five different spinocerebellar ataxia loci: correlation and alternative explanations for disease pathogenesis. Mol Cells. 2007;24:338-42 pubmed
    ..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 ..
  71. Bettencourt C, Santos C, Montiel R, Costa M, Cruz Morales P, Santos L, et al. Increased transcript diversity: novel splicing variants of Machado-Joseph disease gene (ATXN3). Neurogenetics. 2010;11:193-202 pubmed publisher
    ..MJD is caused by an expansion of a CAG tract at exon 10 of the ATXN3 gene (14q32.1), which encodes for ataxin-3...
  72. Todi S, Winborn B, Scaglione K, Blount J, Travis S, Paulson H. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J. 2009;28:372-82 pubmed publisher
    ..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...
  73. Wang H, Ying Z, Wang G. Ataxin-3 regulates aggresome formation of copper-zinc superoxide dismutase (SOD1) by editing K63-linked polyubiquitin chains. J Biol Chem. 2012;287:28576-85 pubmed publisher
    ..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. ..