PXD003446

PXD003446 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2016-01-11 07:53:28	ID requested
⏵ 1	2017-01-31 03:46:42	announced

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]

curator keyword: Biomedical

submitter keyword: Huntington's disease, Proteomics, Interactions

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

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/2017/01/PXD003446

PRIDE project URI

• PRIDE
  1. PXD003446
     1. Label: PRIDE project
     2. Name: A Multiple Hit Model for the Diverse Pathogenic Effects Specific to Huntingtin Aggregate Stage in Cells