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PXD054817

PXD054817 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMultidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal and malignant urothelial cells
DescriptionEpigenetic regulators, such as the SWI/SNF complex, play an important role in tissue development and homeostasis, and are frequently mutated in cancer. ARID1A, a subunit of the SWI/SNF complex, is mutated in approximately 20% of all bladder tumors, however, our understanding of the consequences thereof remains limited. Finding truncations to be the most common mutation, we generated loss- and gain-of-function models to conduct RNA-Seq, interactome analyses, Omni-ATAC-Seq, and first functional studies to characterize ARID1A-affected pathways potentially suitable for the treatment of ARID1A-deficient bladder cancers. We observed decreased cell proliferation and deregulation of stress-regulated pathways, including DNA repair in ARID1A-deficient cells. Furthermore, ARID1A was linked to alternative splicing and translational regulation on RNA and interactome levels. ARID1A deficiency drastically reduced the accessibility of chromatin, especially around introns and distal, but not proximal, enhancers. Less accessible chromatin areas were mapped to pathways such as cell proliferation and DNA damage response. Indeed, the G2/M checkpoint appeared impaired after DNA damage in ARID1A-deficient cells. Together, this highlights the broad impact of ARID1A and the possibility of targeting proliferative and DNA repair pathways.
HostingRepositoryPRIDE
AnnounceDate2025-03-02
AnnouncementXMLSubmission_2025-03-02_07:50:42.475.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristian Preisinger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-08-12 09:09:22ID requested
12025-03-02 07:50:42announced
Publication List
10.1002/1878-0261.70019;
Keyword List
submitter keyword: human,AP-MS, urothelial cell lines
Contact List
Dr. Christian Preisinger
contact affiliationIZKF Aachen Meduical Faculty University Clinic RWTH Aachen
contact emailcpreisinger@ukaachen.de
lab head
Christian Preisinger
contact affiliationProteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact emailcpreisinger@ukaachen.de
dataset submitter
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Dataset FTP location
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