PXD054817

PXD054817 is an original dataset announced via ProteomeXchange.

Title	Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal and malignant urothelial cells
Description	Epigenetic 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.
HostingRepository	PRIDE
AnnounceDate	2025-03-02
AnnouncementXML	Submission_2025-03-02_07:50:42.475.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Preisinger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-12 09:09:22	ID requested
⏵ 1	2025-03-02 07:50:42	announced

10.1002/1878-0261.70019;

submitter keyword: human,AP-MS, urothelial cell lines

Dr. Christian Preisinger
contact affiliation	IZKF Aachen Meduical Faculty University Clinic RWTH Aachen
contact email	cpreisinger@ukaachen.de
lab head
Christian Preisinger
contact affiliation	Proteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact email	cpreisinger@ukaachen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054817
     1. Label: PRIDE project
     2. Name: Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal and malignant urothelial cells