PXD020428

PXD020428 is an original dataset announced via ProteomeXchange.

Title	Glutathionylation decreases methyltransferase activity of PRMT5 and inhibits cell proliferation
Description	Glutathionylation is an important posttranslational modification that protects proteins from further oxidative damage as well as influencing protein structure and activity. In the present study, we demonstrate that the cysteine-42 residue in protein arginine N-methyltransferase 5 (PRMT5) is glutathionylated in aged mice or in cells that have been exposed to oxidative stress. Deglutathionylation of this protein is catalyzed by glutaredoxin-1 (Grx1). Using mutagenesis and subsequent biochemical analyses, we show that glutathionylation decreased the binding affinity of PRMT5 with methylosome protein-50 (MEP50) and reduced the methyltransferase activity of PRMT5. Furthermore, overexpression of PRMT5-C42A mutant caused a significant increase in histone methylation in HEK293T and A549 cells and promoted cell growth, whereas overexpression of the PRMT5-C42D mutant, a mimic of glutathionylated PRMT5, inhibited cell proliferation. Taken together, our results demonstrate a new mechanism of regulation of PRMT5 methyltransferases activity and suggest that PRMT5 glutathionylation is partly responsible for reactive oxygen species-mediated cell growth inhibition
HostingRepository	PRIDE
AnnounceDate	2020-09-02
AnnouncementXML	Submission_2020-09-02_01:21:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meiqi Yi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-18 16:29:01	ID requested
⏵ 1	2020-09-02 01:21:49	announced

Yi M, Ma Y, Chen Y, Liu C, Wang Q, Deng H, Glutathionylation Decreases Methyltransferase Activity of PRMT5 and Inhibits Cell Proliferation. Mol Cell Proteomics, 19(11):1910-1920(2020) [pubmed]

submitter keyword: reactive oxygen species (ROS), glutathionylation, protein arginine N-methyltransferase 5 (PRMT5), methyltransferase activity, binding affinity

Haiteng Deng
contact affiliation	Tsinghua University
contact email	dht@mail.tsinghua.edu.cn
lab head
Meiqi Yi
contact affiliation	Tsinghua University
contact email	yimq15@mails.tsinghua.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020428
     1. Label: PRIDE project
     2. Name: Glutathionylation decreases methyltransferase activity of PRMT5 and inhibits cell proliferation