PXD014799

PXD014799 is an original dataset announced via ProteomeXchange.

Title	PRMT1 controls the Senescence Associated Secretory Phenotype in Replication Stress Response
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:58:50.025.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Enrico Massignani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylated residue; dimethylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-29 02:00:37	ID requested
1	2020-01-15 02:52:03	announced
⏵ 2	2024-10-22 04:58:50	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: PRMT1, SASP, replication stress response,Arginine methylation

Tiziana Bonaldi
contact affiliation	Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan 20139, Italy
contact email	tiziana.bonaldi@ieo.it
lab head
Enrico Massignani
contact affiliation	European Institute of Oncology IRCSS, Department of Experimental Oncology, Milan, Italy
contact email	enrico.massignani@ieo.it
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/2020/01/PXD014799

PRIDE project URI

• PRIDE
  1. PXD014799
     1. Label: PRIDE project
     2. Name: PRMT1 controls the Senescence Associated Secretory Phenotype in Replication Stress Response