PXD048501-1

PXD048501 is an original dataset announced via ProteomeXchange.

Title	Targeted approach to determine the impact of cancer-associated protease variants
Description	Several mechanisms of cancer progression, from tumour onset to metastasis, critically involve proteolytic activity. Studying the role of proteases in cancer, it is important to consider single nucleotide variants (SNVs) affecting the active site of proteases, that might impact cleavage specificity, substrate processing and thus cancer cell behaviour. To facilitate systematic studies, we here present a targeted approach to determine the impact of cancer-associated protease variants (TACAP). Starting with the semi-automated identification of potential specificity-modulating SNVs, our workflow comprises mass spectrometry-based cleavage specificity profiling and substrate identification, localisation and inhibitor studies, followed by functional analyses investigating cancer cell migration. We demonstrate the feasibility of TACAP by analysing the meprin β R238Q variant. The amino acid exchange R238Q leads to a loss of meprin β’s characteristic cleavage preference for acidic amino acids at the P1’ position, accompanied with changes in substrate pool and inhibitor affinity compared to meprin β wildtype.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_14:06:13.633.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Tholey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-12 03:05:29	ID requested
⏵ 1	2025-05-06 14:06:14	announced

10.1126/sciadv.adp5958;

Bickenbach K, David N, Koudelka T, Joos C, Scharfenberg F, R, ü, ffer M, Armbrust F, Georgiadis D, Beau F, Stahmer L, Rahn S, Tholey A, Pietrzik C, Becker-Pauly C, Targeted approach to determine the impact of cancer-associated protease variants. Sci Adv, 11(7):eadp5958(2025) [pubmed]

submitter keyword: SNVs, meprin β, proteases,cancer, migration, spheroids, cancer-associated variants, cleavage specificity, N-terminomics, organotypic brain slices

Prof. Dr. Andreas Tholey
contact affiliation	Systematische Proteomics & Bioanalytik - Institut für Experimentelle Medizin Christian-Albrechts-Universität zu Kiel Niemannsweg 11 24105 Kiel, Germany
contact email	a.tholey@iem.uni-kiel.de
lab head
Andreas Tholey
contact affiliation	Systematic Proteome Research & Bioanalytics, University of Kiel
contact email	a.tholey@iem.uni-kiel.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/2025/05/PXD048501

PRIDE project URI

• PRIDE
  1. PXD048501
     1. Label: PRIDE project
     2. Name: Targeted approach to determine the impact of cancer-associated protease variants