Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

  1. Laidou, Stamatia
  2. Alanis-Lobato, Gregorio ORCID logo
  3. Pribyl, Jan
  4. Raskó, Tamás
  5. Tichy, Boris ORCID logo
  6. Mikulasek, Kamil ORCID logo
  7. Tsagiopoulou, Maria ORCID logo
  8. Oppelt, Jan ORCID logo
  9. Kastrinaki, Georgia ORCID logo
  10. Lefaki, Maria
  11. Singh, Manvendra ORCID logo
  12. Zink, Annika ORCID logo
  13. Chondrogianni, Niki ORCID logo
  14. Psomopoulos, Fotis ORCID logo
  15. Prigione, Alessandro
  16. Ivics, Zoltan ORCID logo
  17. Pospisilova, Sarka ORCID logo
  18. Skládal, Petr ORCID logo
  19. Izsvak, Zsuzsanna ORCID logo
  20. Andrade-Navarro, Miguel A.
  21. Petrakis, Spyros ORCID logo

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WeightNameValue
1000 Titel
  • Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery
1000 Autor/in
  1. Laidou, Stamatia |
  2. Alanis-Lobato, Gregorio |
  3. Pribyl, Jan |
  4. Raskó, Tamás |
  5. Tichy, Boris |
  6. Mikulasek, Kamil |
  7. Tsagiopoulou, Maria |
  8. Oppelt, Jan |
  9. Kastrinaki, Georgia |
  10. Lefaki, Maria |
  11. Singh, Manvendra |
  12. Zink, Annika |
  13. Chondrogianni, Niki |
  14. Psomopoulos, Fotis |
  15. Prigione, Alessandro |
  16. Ivics, Zoltan |
  17. Pospisilova, Sarka |
  18. Skládal, Petr |
  19. Izsvak, Zsuzsanna |
  20. Andrade-Navarro, Miguel A. |
  21. Petrakis, Spyros |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-02-11
1000 Erschienen in
1000 Quellenangabe
  • 32:101458
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1016/j.redox.2020.101458 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058924/ |
1000 Ergänzendes Material
  • https://www.sciencedirect.com/science/article/pii/S2213231719312947?via%3Dihub#appsec1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expression of the mutant protein. We characterized the structure and the protein composition of insoluble polyQ IIBs which gradually occupy the nuclei and are responsible for the generation of reactive oxygen species. In response to their formation, our transcriptome analysis reveals a cerebellum-specific perturbed protein interaction network, primarily affecting protein synthesis. We propose that insoluble polyQ IIBs cause oxidative and nucleolar stress and affect the assembly of the ribosome by capturing or down-regulating essential components. The inducible cell system can be utilized to decipher the cellular consequences of polyQ protein aggregation. Our strategy provides a broadly applicable methodology for studying polyQ diseases.
1000 Sacherschließung
lokal Ribosome
lokal Polyglutamine
lokal Ataxin-1
lokal Oxidative stress
gnd 4233582-6 Transposon
lokal Sleeping beauty transposon
lokal Protein network
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/TGFpZG91LCBTdGFtYXRpYSAgIA==|https://orcid.org/0000-0001-9339-4229|https://frl.publisso.de/adhoc/uri/IFByaWJ5bCwgSmFuICAgIA==|https://frl.publisso.de/adhoc/uri/IFJhc2vDsywgVGFtw6FzICAgICA=|https://orcid.org/0000-0001-9252-7974|https://orcid.org/0000-0002-6415-1284|https://orcid.org/0000-0002-1653-0327|https://orcid.org/0000-0002-3076-4840|https://orcid.org/0000-0002-0373-3117|https://frl.publisso.de/adhoc/uri/IExlZmFraSwgTWFyaWEgICAgIA==|https://orcid.org/0000-0002-8626-5418|https://orcid.org/0000-0002-8489-6339|https://orcid.org/0000-0002-5867-0862|https://orcid.org/0000-0002-0222-4273|https://frl.publisso.de/adhoc/uri/UHJpZ2lvbmUsIEFsZXNzYW5kcm8=|https://orcid.org/0000-0002-7803-6658|https://orcid.org/0000-0002-8966-4887|https://orcid.org/0000-0002-3868-5725|https://orcid.org/0000-0002-2053-2384|https://frl.publisso.de/adhoc/uri/ICAgIEFuZHJhZGUtTmF2YXJybywgTWlndWVsIEEuICA=|https://orcid.org/0000-0001-9094-3480
1000 Label
1000 Förderer
  1. Horizon 2020 |
  2. Hellenic Foundation for Research and Innovation |
  3. General Secretariat for Research and Technology |
  4. Ministerstvo Školství, Mládeže a Tělovýchovy |
  5. Národní centrum lékařské genomiky |
  6. Ministerstvo Školství, Mládeže a Tělovýchovy |
  7. European Regional Development Fund |
  8. Bundesministerium für Bildung und Forschung |
1000 Fördernummer
  1. 692298
  2. -
  3. 122
  4. LM2018127
  5. LM2018132
  6. e-INFRA LM2018140
  7. CZ.02.1.01/0.0/0.0/16_013/0001776
  8. AZ.031A318
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. CIISB research infrastructure project
  5. Research infrastructure project
  6. e-Infrastruktura CZ
  7. CIISB4HEALTH
  8. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Horizon 2020 |
    1000 Förderprogramm -
    1000 Fördernummer 692298
  2. 1000 joinedFunding-child
    1000 Förderer Hellenic Foundation for Research and Innovation |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer General Secretariat for Research and Technology |
    1000 Förderprogramm -
    1000 Fördernummer 122
  4. 1000 joinedFunding-child
    1000 Förderer Ministerstvo Školství, Mládeže a Tělovýchovy |
    1000 Förderprogramm CIISB research infrastructure project
    1000 Fördernummer LM2018127
  5. 1000 joinedFunding-child
    1000 Förderer Národní centrum lékařské genomiky |
    1000 Förderprogramm Research infrastructure project
    1000 Fördernummer LM2018132
  6. 1000 joinedFunding-child
    1000 Förderer Ministerstvo Školství, Mládeže a Tělovýchovy |
    1000 Förderprogramm e-Infrastruktura CZ
    1000 Fördernummer e-INFRA LM2018140
  7. 1000 joinedFunding-child
    1000 Förderer European Regional Development Fund |
    1000 Förderprogramm CIISB4HEALTH
    1000 Fördernummer CZ.02.1.01/0.0/0.0/16_013/0001776
  8. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm -
    1000 Fördernummer AZ.031A318
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6432696.rdf
1000 Erstellt am 2022-03-30T11:13:23.597+0200
1000 Erstellt von 323
1000 beschreibt frl:6432696
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2022-05-02T08:11:38.219+0200
1000 Objekt bearb. Mon May 02 08:11:25 CEST 2022
1000 Vgl. frl:6432696
1000 Oai Id
  1. oai:frl.publisso.de:frl:6432696 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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