PXD010161-1

PXD010161 is an original dataset announced via ProteomeXchange.

Title	Proteome and ubiquitinome changes in Huntington’s disease
Description	Huntington’s disease is caused by a polyglutamine repeat expansion at the N-terminus of the huntingtin protein which affects the function and folding of the protein, and results in intracellular protein aggregates. Here, we examined whether this mutation leads to altered ubiquitination of huntingtin and other proteins in both soluble and insoluble fractions of brain lysates of the Q175 knock-in Huntington disease mouse model and the Q20 wild-type mouse model. Ubiquitination sites are detected by identification of Gly-Gly (diGly) remnant motifs that remain on modified lysine residues after digestion. We identified K6, K9, K132, K804 and K837 as endogenous ubiquitination sites of soluble huntingtin, with wild-type huntingtin being mainly ubiquitinated at K132, K804 and K837. Mutant huntingtin protein levels were strongly reduced in the soluble fraction while K6 and K9 were mainly ubiquitinated. In the insoluble fraction increased levels of huntingtin K6 and K9 diGly sites were observed for mutant huntingtin as compared to wild type. Besides huntingtin, proteins with various roles, including membrane organization, transport, mRNA processing, gene transcription, translation, catabolic processes and oxidative phosphorylation, were differently expressed or ubiquitinated in wild-type and mutant huntingtin brain tissues. Correlating protein and diGly site fold-changes in the soluble fraction revealed that diGly site abundances of the majority of the proteins were not related to protein fold-changes, indicating that these proteins were differentially ubiquitinated in the Q175 mice. In contrast, both the fold-change of the protein level and diGly site level were increased for several proteins in the insoluble fraction, including ubiquitin, ubiquilin-2, sequestosome-1/p62 and myo5a. Our data sheds light on putative novel proteins involved in different cellular processes as well as their ubiquitination status in Huntington’s disease, which forms the basis for further mechanistic studies to understand the role of differential ubiquitination of huntingtin as well as ubiquitin-regulated processes in Huntington’s disease.
HostingRepository	PRIDE
AnnounceDate	2019-06-05
AnnouncementXML	Submission_2019-06-05_09:05:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arzu Tugce Guler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-19 01:05:39	ID requested
⏵ 1	2019-06-05 09:05:07	announced
2	2024-10-22 04:54:56	announced	2024-10-22: Updated project metadata.

Sap KA, Guler AT, Bezstarosti K, Bury AE, Juenemann K, Demmers JA, Reits EA, Global Proteome and Ubiquitinome Changes in the Soluble and Insoluble Fractions of Q175 Huntington Mice Brains. Mol Cell Proteomics, 18(9):1705-1720(2019) [pubmed]

submitter keyword: Huntington, Mouse, Brain, Ubiquitination, diGly, PTMs, LFQ

Eric A. Reits
contact affiliation	Professor Cellular Imaging, Huntington degradation research groupleader Department of Medical Biology, Amsterdam UMC (AMC), Meibergdreef 15, 1105AZ Amsterdam, the Netherlands
contact email	e.a.reits@amc.uva.nl
lab head
Arzu Tugce Guler
contact affiliation	Academisch Medisch Centrum
contact email	a.t.guler@amc.uva.nl
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/2019/06/PXD010161

PRIDE project URI

• PRIDE
  1. PXD010161
     1. Label: PRIDE project
     2. Name: Proteome and ubiquitinome changes in Huntington’s disease