PXD009070

PXD009070 is an original dataset announced via ProteomeXchange.

Title	Proteomics Profiling of Arginine Methylation Defines PRMT5 Substarate Specificity
Description	Protein arginine methyltransferases (PRMTs) catalyze arginine methylation, an abundant post-translational modification occurring on both chromatin-bound and cytoplasmic proteins. Growing evidence supports the involvement of PRMT5, the major Type II PRMT, in pro-survival and differentiation pathways, important during development and to promote tumorigenesis. Thus, PRMT5 emerges as an attractive drug target and inhibitors are currently in clinical trials for cancer therapy. However, the knowledge of PRMT5 non-histone substrates is still limited, as are the dynamic changes in methylation levels upon its inhibition. Here, we employed a newly established pipeline coupling SILAC with methyl-peptides immuno-enrichment to globally profile arginine methylation following PRMT5 inhibition by GSK591 and adopted the heavy-methyl SILAC as orthogonal validation method to reduce false discovery rate. Then, in vitro methylation assays on a set of PRMT5 targets provided novel mechanistic insights into its strict preference to methylate arginine sandwiched between two neighbouring glycines (GRG). In conclusion, we identified novel PRMT5 substrates, thus providing the first proof of concept of the in vivo efficacy of PRMT5 inhibitor that impacts on arginine methylation beyond histones.
HostingRepository	PRIDE
AnnounceDate	2019-04-10
AnnouncementXML	Submission_2019-04-10_11:50:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	alessandro cuomo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; dimethylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-28 07:19:19	ID requested
1	2019-04-10 07:00:53	announced
⏵ 2	2019-04-10 11:50:58	announced	Updated publication reference for PubMed record(s): 30940768.

Musiani D, Bok J, Massignani E, Wu L, Tabaglio T, Ippolito MR, Cuomo A, Ozbek U, Zorgati H, Ghoshdastider U, Robinson RC, Guccione E, Bonaldi T, Proteomics profiling of arginine methylation defines PRMT5 substrate specificity. Sci Signal, 12(575):(2019) [pubmed]

submitter keyword: LC-MS, PRMT5, Arginine methylation

Tiziana Bonaldi
contact affiliation	Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
contact email	tiziana.bonaldi@ieo.it
lab head
alessandro cuomo
contact affiliation	IEO
contact email	alessandro.cuomo@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/2019/04/PXD009070

PRIDE project URI

• PRIDE
  1. PXD009070
     1. Label: PRIDE project
     2. Name: Proteomics Profiling of Arginine Methylation Defines PRMT5 Substarate Specificity