PXD027130

PXD027130 is an original dataset announced via ProteomeXchange.

Title	Proteome profiling of RNF213 depleted cells reveals nitric oxide regulator DDAH1 antilisterial activity
Description	RNF213 is a large, poorly characterized interferon-induced protein. Mutations in RNF213 are associated with predisposition for Moyamoya disease (MMD), a rare cerebrovascular disorder. Recently, RNF213 was found to have broad antimicrobial activity in vitro and in vivo, yet the molecular mechanisms behind this function remain unclear. Using mass spectrometry-based proteomics and validation by real-time PCR we here report that knockdown of RNF213 leads to transcriptional upregulation of MVP and downregulation of CYR61, in line with reported pro- and anti-bacterial activities of these proteins. Knockdown of RNF213 also results in downregulation of DDAH1, which we discover to exert anti-microbial activity against Listeria monocytogenes infection. DDAH1 regulates production nitric oxide (NO), a molecule with both vascular and antimicrobial effects. We show that NO production is reduced in macrophages from RNF213 KO mice, suggesting that RNF213 controls Listeria infection through regulation of DDAH1 transcription and production of NO. Our findings propose a potential mechanism for the antilisterial activity of RNF213 and highlight NO as a potential link between RNF213-mediated immune responses and the development of MMD.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_05:01:36.273.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabien Thery
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-06 08:37:03	ID requested
⏵ 1	2022-02-17 05:01:37	announced

Martina L, Asselman C, Thery F, Boucher K, Delhaye L, Maia TM, Dermaut B, Eyckerman S, Impens F, Proteome Profiling of RNF213 Depleted Cells Reveals Nitric Oxide Regulator DDAH1 Antilisterial Activity. Front Cell Infect Microbiol, 11():735416(2021) [pubmed]

submitter keyword: Human, infection, bacteria, Listeria, Listeria monocytogenes, nitric oxide, RNF213, DDAH1

Francis Impens
contact affiliation	VIB proteomics core, Ghent; VIB-UGent Center for Medical Biotechnology, Ghent; Department of Biomolecular Medicine, Ghent University.
contact email	francis.impens@vib-ugent.be
lab head
Fabien Thery
contact affiliation	VIB-UGent
contact email	fabien.thery91@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027130
     1. Label: PRIDE project
     2. Name: Proteome profiling of RNF213 depleted cells reveals nitric oxide regulator DDAH1 antilisterial activity