PXD050527

PXD050527 is an original dataset announced via ProteomeXchange.

Title	MS-based analysisi of the role of protein neddylation in the context of T-cell-mediated anti-tumor immunity (1)
Description	Neddylation is one type of post-translational modification (PTM) by which the ubiquitin-like molecule NEDD8 is covalently attached to protein substrates, in a process that depends on NAE1 (NEDD8 activating enzyme E1 regulatory subunit). Here we study the role of protein neddylation in the context of T-cell-mediated anti-tumor immunity. Analysis of publicly available single-cell RNA sequencing databases revealed that tumor infiltrating lymphocytes (TILs) upregulate the expression of Nedd8 during their differentiation into effector memory cells. In vitro activation of mouse and human CD8+ T cells drives the upregulation of the neddylation pathway, resulting in an enrichment of neddylated proteins. In vivo tumor challenge assays demonstrated that CD8+ T cells lacking NAE1 (NAE1-KO) have a reduced anti-tumor capacity, and display a less activated phenotype with impaired differentiation into effector T cells. LC MS/MS proteomic analyses conducted on activated NAE1-KO CD8+ T cells and on CD8+ T cells subjected to the treatment of neddylation inhibitor MLN4924 elucidated a pronounced impairment in both glycolytic and oxidative phosphorylation metabolic pathways. In this context, we validated three novel NEDD8 interactors (LDHA, HK1 and ENOA), which are relevant enzymes in the glycolytic pathway. This can clarify the role of neddylation in the metabolic shift to glycolysis exerted by CD8+ T cells during their anti-tumor activity.
HostingRepository	PRIDE
AnnounceDate	2025-04-15
AnnouncementXML	Submission_2025-04-15_00:24:41.649.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050527
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	neddylated lysine
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-11 04:15:00	ID requested
⏵ 1	2025-04-15 00:24:42	announced

10.6019/PXD050527;

submitter keyword: mass spectrometry, NAE1,Nedd8, MLN4924

Felix Elortza
contact affiliation	Proteomics Service CIC bioGUNE Bizkaia Tech. Park Build. 800 48160 Derio Spain
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050527
     1. Label: PRIDE project
     2. Name: MS-based analysisi of the role of protein neddylation in the context of T-cell-mediated anti-tumor immunity (1)