| LAIDOU, Stamatia, Gregorio ALANIS-LOBATO, Jan PŘIBYL, Tamás RASKÓ, Boris TICHÝ, Kamil MIKULÁŠEK, Maria TSAGIOPOULOU, Jan OPPELT, Georgia KASTRINAKI, Maria LEFAKI, Manvendra SINGH, Annika ZINK, Niki CHONDROGIANNI, Fotis PSOMOPOULOS, Alessandro PRIGIONE, Zoltan IVICS, Šárka POSPÍŠILOVÁ, Petr SKLÁDAL, Zsuzsanna IZSVAK, Miguel A. ANDRADE-NAVARRO and Spyros PETRAKIS. Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery. Redox Biology. Amsterdam: Elsevier, 2020, vol. 32, MAY 2020, p. 1-16. ISSN 2213-2317. Available from: https://dx.doi.org/10.1016/j.redox.2020.101458. |
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@article{1689437,
author = {Laidou, Stamatia and AlanisandLobato, Gregorio and Přibyl, Jan and Raskó, Tamás and Tichý, Boris and Mikulášek, Kamil and Tsagiopoulou, Maria and Oppelt, Jan and Kastrinaki, Georgia and Lefaki, Maria and Singh, Manvendra and Zink, Annika and Chondrogianni, Niki and Psomopoulos, Fotis and Prigione, Alessandro and Ivics, Zoltan and Pospíšilová, Šárka and Skládal, Petr and Izsvak, Zsuzsanna and AndradeandNavarro, Miguel A. and Petrakis, Spyros},
article_location = {Amsterdam},
article_number = {MAY 2020},
doi = {http://dx.doi.org/10.1016/j.redox.2020.101458},
keywords = {Ataxin-1; Polyglutamine; Sleeping beauty transposon; Oxidative stress; Protein network; Ribosome},
language = {eng},
issn = {2213-2317},
journal = {Redox Biology},
title = {Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery},
url = {https://doi.org/10.1016/j.redox.2020.101458},
volume = {32},
year = {2020}
}
TY - JOUR
ID - 1689437
AU - Laidou, Stamatia - Alanis-Lobato, Gregorio - Přibyl, Jan - Raskó, Tamás - Tichý, Boris - Mikulášek, Kamil - Tsagiopoulou, Maria - Oppelt, Jan - Kastrinaki, Georgia - Lefaki, Maria - Singh, Manvendra - Zink, Annika - Chondrogianni, Niki - Psomopoulos, Fotis - Prigione, Alessandro - Ivics, Zoltan - Pospíšilová, Šárka - Skládal, Petr - Izsvak, Zsuzsanna - Andrade-Navarro, Miguel A. - Petrakis, Spyros
PY - 2020
TI - Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery
JF - Redox Biology
VL - 32
IS - MAY 2020
SP - 1-16
EP - 1-16
PB - Elsevier
SN - 22132317
KW - Ataxin-1
KW - Polyglutamine
KW - Sleeping beauty transposon
KW - Oxidative stress
KW - Protein network
KW - Ribosome
UR - https://doi.org/10.1016/j.redox.2020.101458
L2 - https://doi.org/10.1016/j.redox.2020.101458
N2 - 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.
ER -
LAIDOU, Stamatia, Gregorio ALANIS-LOBATO, Jan PŘIBYL, Tamás RASKÓ, Boris TICHÝ, Kamil MIKULÁŠEK, Maria TSAGIOPOULOU, Jan OPPELT, Georgia KASTRINAKI, Maria LEFAKI, Manvendra SINGH, Annika ZINK, Niki CHONDROGIANNI, Fotis PSOMOPOULOS, Alessandro PRIGIONE, Zoltan IVICS, Šárka POSPÍŠILOVÁ, Petr SKLÁDAL, Zsuzsanna IZSVAK, Miguel A. ANDRADE-NAVARRO and Spyros PETRAKIS. Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery. \textit{Redox Biology}. Amsterdam: Elsevier, 2020, vol.~32, MAY 2020, p.~1-16. ISSN~2213-2317. Available from: https://dx.doi.org/10.1016/j.redox.2020.101458.
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