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PXD047613

PXD047613 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA site-specific analysis of the ADP-Ribosylome unveils Homogeneous Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast Cancer cell lines
DescriptionADP-ribosylation (ADPr) signaling plays a crucial role in the DNA damage response. Inhibitors against the main enzyme catalyzing ADPr after DNA damage – PARP1 – are used as targeted therapies against breast cancers with BRCA1/2 mutations. However, development of resistance to PARP inhibitors (PARPi) is a major obstacle in treating patients. To better understand the role of ADPr in PARPi sensitivity, we used Liquid Chromatography-Mass Spectrometry (LC-MS) for systems level analysis of the ADP-ribosylome in six breast cancer cell lines with different PARPi sensitivities. We identified 1632 sites on 777 proteins, primarily on serine residues, with a high site overlap of DNA damage-related proteins across all cell lines, demonstrating high conservation in ADPr signaling after DNA damage. We furthermore observed site-specific differences in ADPr intensities in PARPi-sensitive BRCA mutants, and unique ADPr sites in PARPi-resistant BRCA mutant cells, which we notably show to have low PARG levels and longer PARP1 ADPr chains.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:52:13.173.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHolda Anagho
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListadenosine diphosphoribosyl (ADP-ribosyl) modified residue
InstrumentOrbitrap Fusion Lumos; Orbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-12-07 05:49:46ID requested
12024-08-02 07:52:17announced
22024-10-22 06:52:13announced2024-10-22: Updated project metadata.
Publication List
10.1016/J.CELREP.2024.114433;
Keyword List
submitter keyword: proteomics, mass spectrometry, EThcD, PARP inhibitor sensitivity, PARP, Af1521 macrodomain, ADP-ribosylome, PARG,ADP-ribosylation
Contact List
Michael Lund Nielsen
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailmichael.lund.nielsen@cpr.ku.dk
lab head
Holda Anagho
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
contact emailholda.anagho@cpr.ku.dk
dataset submitter
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