PXD009072

PXD009072 is an original dataset announced via ProteomeXchange.

Title	Changes in the human platelet protein ubiquitylation landscape following GPVI activation
Description	Platelet activators stimulate post-translational modification of signalling proteins to change their activity or their molecular interactions leading to signal propagation. One covalent modification is attachment of the small protein ubiquitin to lysine residues in target proteins. Modification by ubiquitin can either target proteins for degradation by the proteasome or act as a scaffold for other proteins. Pharmacological inhibition of deubiquitylases or the proteasome inhibits platelet activation by collagen, demonstrating a role for ubiquitylation, but relatively few substrates for ubiquitin have been identified and the molecular basis of inhibition is not established. Here we report the ubiquitome of human platelets and changes in ubiquitylated proteins following stimulation by collagen related peptide (CRP-XL). We identified 1634 ubiquitylated peptides derived from 691 proteins, revealing extensive ubiquitylation in resting platelets. 925 of these peptides show an increase of more than 2-fold following stimulation with CRP-XL. Multiple sites of ubiquitylation were identified on a number of proteins including Syk, filamin and integrins. Adhesion and spreading on fibrinogen mediated by the major platelet integrin IIb3 is blocked by inhibition of deubiquitylases. This work reveals extensive protein ubiquitylation during activation of human platelets and opens the possibility of novel therapeutic interventions targeting the ubiquitin machinery.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:43:31.204.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009072
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Benedikt Kessler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-28 07:30:58	ID requested
1	2019-01-07 02:11:35	announced
⏵ 2	2024-10-22 04:43:33	announced	2024-10-22: Updated project metadata.

10.6019/PXD009072;

10.1055/s-0038-1676344;

Unsworth AJ, Bombik I, Pinto-Fernandez A, McGouran JF, Konietzny R, Zahedi RP, Watson SP, Kessler BM, Pears CJ, Human Platelet Protein Ubiquitylation and Changes following GPVI Activation. Thromb Haemost, 119(1):104-116(2019) [pubmed]

curator keyword: Biological

submitter keyword: proteomics,Platelet activation, mass spectrometry, ubiquitome, Syk, ubiquitin

Benedikt M Kessler
contact affiliation	Target Discovery Institute Nuffield Department of Medicine University of Oxford Roosevelt Drive Oxford OX3 7FZ UK Tel: +44 (0) 1865 612 921 Email: benedikt.kessler@ndm.ox.ac.uk Website: www.tdi.ox.ac.uk/mass-spectrometry
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Benedikt Kessler
contact affiliation	University of Oxford
contact email	kesslerbenedikt@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009072
     1. Label: PRIDE project
     2. Name: Changes in the human platelet protein ubiquitylation landscape following GPVI activation