PXD009199

PXD009199 is an original dataset announced via ProteomeXchange.

Title	Mapping Ubiquitination Sites in Alzheimer's Disease
Description	Alzheimer’s Disease (AD) is characterized by the deposition of protein aggregates such as neurofibrillary tangles (NFTs) and amyloid (Aβ) plaques in the brain. Post-translational modification through ubiquitylationplays critical roles in clearing misfolded protein aggregates. Investigating global ubiquitylation changes inAD brain may provide insights regarding the underlying mechanisms of proteostasis and disease pathogenesis.Here, we utilizedan immunoaffinity approach to specifically enrichubiquitinated(di-glycine) peptides frompostmortemhuman control and AD braintissues.Mass spectrometry(MS)based proteomicanalysis identified global ubiquitylation changes associated with ADand hierarchical clustering of the human brain ubiquitylome clearly classified AD cases from healthy controls based on ubiquitylation patterns. Polyubiquitin linkage analysis identified increased levels of all seven polyubiquitin linkage typesas well as total ubiquitin in the AD brain tissues.We also report novel ubiquitylation sites in the microtubulebinding repeatof Tauwith potential implicationsfor Tauaggregation. Dually modified peptides with both phosphorylation and ubiquitylationsites, many of which originated from Tauprotein are also differentially enriched in AD.Furthermore, all the KXGS motifswithin themicrotubule binding region (MTBR)of Tauprotein,which represents the core ofNFTs,are enriched among dually modified peptides. Collectively, these studieshighlight the utility of an immunoaffinity enrichment approach coupled with MSanalysis for mapping AD associated global ubiquitylome changesas well as to gain insights intounderlying proteostasis pathwaysaltered in AD brain.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:43:43.676.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Dammer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-13 08:18:12	ID requested
1	2019-06-25 03:18:22	announced
⏵ 2	2024-10-22 04:43:51	announced	2024-10-22: Updated project metadata.

10.1002/pmic.201800108;

Abreha MH, Dammer EB, Ping L, Zhang T, Duong DM, Gearing M, Lah JJ, Levey AI, Seyfried NT, Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease. Proteomics, 18(20):e1800108(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: ubiquitylome,AD, GG remnant peptides

Nicholas T. Seyfried
contact affiliation	Emory University School of Medicine Department of Biochemistry
contact email	nseyfri@emory.edu
lab head
Eric Dammer
contact affiliation	Emory University
contact email	edammer@emory.edu
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/PXD009199

PRIDE project URI

• PRIDE
  1. PXD009199
     1. Label: PRIDE project
     2. Name: Mapping Ubiquitination Sites in Alzheimer's Disease