PXD031192-1

PXD031192 is an original dataset announced via ProteomeXchange.

Title	Repression of PRMT5-mediated dimethylation stabilizes vimentin and promotes metastasis in MTAP-loss lung cancer
Description	Abstract The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis, and patients with low MTAP expression displayed worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduced the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. Vimentin was revealed as a novel dimethyl-protein with less dimethylation level in response to MTAP loss. The sDMA modification on vimentin reduces its protein abundance and trivially affects its filamentous structure. In MTAP-loss cells, lower sDMA level prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin, contributing to cell invasion. This inverse association of the MTAP/PRMT5 axis with vimentin proteins was clinically corroborated. Taken together, we propose a novel mechanism of vimentin post-translational regulation and provide new insights in metastasis.
HostingRepository	PRIDE
AnnounceDate	2022-05-31
AnnouncementXML	Submission_2022-05-31_00:22:31.003.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031192
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yi-Ju Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; dimethylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-24 02:47:58	ID requested
⏵ 1	2022-05-31 00:22:31	announced

Dataset with its publication pending

submitter keyword: Human, lung cancer, dimethylation

Yi-Ju Chen
contact affiliation	Institute of Chemistry, Academia Sinica, Taiwan
contact email	tp7249@gate.sinica.edu.tw
lab head
Yi-Ju Chen
contact affiliation	Academia Sinica
contact email	tp7249@gate.sinica.edu.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031192
     1. Label: PRIDE project
     2. Name: Repression of PRMT5-mediated dimethylation stabilizes vimentin and promotes metastasis in MTAP-loss lung cancer