PXD012709

PXD012709 is an original dataset announced via ProteomeXchange.

Title	PolyQ-expanded ataxin-1 formed insoluble protein inclusions perturbing translation in a spinocerebellar ataxia type-1 model
Description	Spinocerebellar ataxia type-1 is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1 protein. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are linked to neuronal death. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1. Using an inducible Sleeping Beauty transposon system, we overexpressed ATXN1Q82 gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects of the mutant protein. We characterized the structure and the protein composition of insoluble polyQ IIBs which gradually occupy the nuclei. In response to their formation, our transcriptome analysis reveals a cerebellum-specific perturbed protein interaction network, primarily affecting protein translation. Our study resolves the previously unknown architecture of insoluble polyQ IIBs and suggests that they affect the assembly and the function of the ribosome. Our inducible cell system faithfully models a human cerebellum at the end-stage of the disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:52:53.607.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kamil Mikulasek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	impact II

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-14 02:44:30	ID requested
1	2020-02-18 07:55:26	announced
2	2020-05-18 06:09:45	announced	2020-05-18: Updated publication reference for PubMed record(s): 32145456.
⏵ 3	2024-10-22 04:53:01	announced	2024-10-22: Updated project metadata.

Laidou S, Alanis-Lobato G, Pribyl J, Rask, ó T, Tichy B, Mikulasek K, Tsagiopoulou M, Oppelt J, Kastrinaki G, Lefaki M, Singh M, Zink A, Chondrogianni N, Psomopoulos F, Prigione A, Ivics Z, Pospisilova S, Skladal P, Izsv, á, k Z, Andrade-Navarro MA, Petrakis S, Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery. Redox Biol, 32():101458(2020) [pubmed]

10.1016/j.redox.2020.101458;

curator keyword: Biomedical

submitter keyword: Ataxin-1, Sleeping Beauty transposon, protein network, polyglutamine, AFM, ribosome, nucleolus., spinocerebellar ataxia type-1, RNA-seq

Zbynek Zdrahal
contact affiliation	Zbynek Zdrahal, Research group Proteomics, CEITEC-MU, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic
contact email	zdrahal@sci.muni.cz
lab head
Kamil Mikulasek
contact affiliation	Proteomics Core Facility and Research Group Proteomics CEITEC-MU Masaryk University Brno, Czech Republic
contact email	357352@mail.muni.cz
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD012709

PRIDE project URI

• PRIDE
  1. PXD012709
     1. Label: PRIDE project
     2. Name: PolyQ-expanded ataxin-1 formed insoluble protein inclusions perturbing translation in a spinocerebellar ataxia type-1 model