PXD003446 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A Multiple Hit Model for the Diverse Pathogenic Effects Specific to Huntingtin Aggregate Stage in Cells |
Description | Huntington's disease is a fatal neurodegenerative disorder characterized by the aggregation of polyglutamine-expanded huntingtin into oligomers and fibrils. How protein aggregation leads to cellular dysfunction is not well understood. To address this question, we combined in-cell single molecule fluorescence spectroscopy with quantitative proteomics to define how huntingtin engages in aberrant protein interactions during its progressive aggregation. We find that huntingtin interacts preferentially with key components of distinct cellular processes as aggregation proceeds from soluble oligomers to end-stage inclusions. The aberrant interactions of soluble oligomers are highly enriched on RNA-binding proteins and with proteins functioning in ribosome biogenesis, translation, transcription, and vesicle transport. A significant characteristic of these interactors is the presence of extended low-complexity sequence regions. Compared to the soluble aggregates, the interactome of insoluble inclusions is significantly less complex and is enriched in protein quality control components. Our results suggest a 'multiple hit' model for polyglutamine interactions in pathogenesis, with detrimental effects on cell function occurring in an aggregation stage-dependent manner. |
HostingRepository | PRIDE |
AnnounceDate | 2017-01-31 |
AnnouncementXML | Submission_2017-01-31_03:46:41.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mario Oroshi |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive; LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-01-11 07:53:28 | ID requested | |
⏵ 1 | 2017-01-31 03:46:42 | announced | |
Publication List
Kim YE, Hosp F, Frottin F, Ge H, Mann M, Hayer-Hartl M, Hartl FU, Soluble Oligomers of PolyQ-Expanded Huntingtin Target a Multiplicity of Key Cellular Factors. Mol Cell, 63(6):951-64(2016) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Huntington's disease, Proteomics, Interactions |
Contact List
F. Ulrich Hartl |
contact affiliation | Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany |
contact email | uhartl@biochem.mpg.de |
lab head | |
Mario Oroshi |
contact affiliation | Proteomics |
contact email | oroshi@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD003446
- Label: PRIDE project
- Name: A Multiple Hit Model for the Diverse Pathogenic Effects Specific to Huntingtin Aggregate Stage in Cells