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PXD014799

PXD014799 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePRMT1 controls the Senescence Associated Secretory Phenotype in Replication Stress Response
DescriptionThe protein arginine methyltransferase PRMT1 is overexpressed in various human cancers and linked to poor response to therapy. Although various inhibitors targeting its activity are under development, we still do not fully understand how PRMT1 is involved in the cellular processes underpinning tumorigenesis and chemoresistance. Mass spectrometry–based proteomics revealed PRMT1 as a regulator of global arginine methylation changes in response to replicative stress in cancer cells. We show that, upon cisplatin, DNA-dependent protein kinase binds to- and phosphorylates PRMT1, inducing its chromatin recruitment and redirecting its enzymatic activity from soluble protein targets towards the histone substrate Arg3 of histone H4 (H4R3). On chromatin, DNA-PK/PRMT1 axis induces the Senescence-Associated Secretory Phenotype through the deposition of H4R3me2a at the pro-inflammatory gene promoters and by sustaining p65 binding to chromatin. Finally, PRMT1 inhibition reduced the clonogenic outgrowth of ovarian cancer cells exposed to low doses of CDDP and sensitized them to apoptosis. While unravelling a novel role of PRMT1 in replication stress response, our findings suggest the opportunity of targeting PRMT1 to sensitize cancer cells to genotoxic chemotherapeutics.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:58:50.025.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEnrico Massignani
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmethylated residue; dimethylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-07-29 02:00:37ID requested
12020-01-15 02:52:03announced
22024-10-22 04:58:50announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: PRMT1, SASP, replication stress response,Arginine methylation
Contact List
Tiziana Bonaldi
contact affiliationDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan 20139, Italy
contact emailtiziana.bonaldi@ieo.it
lab head
Enrico Massignani
contact affiliationEuropean Institute of Oncology IRCSS, Department of Experimental Oncology, Milan, Italy
contact emailenrico.massignani@ieo.it
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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