PXD070940

PXD070940 is an original dataset announced via ProteomeXchange.

Title	MAP4K2 promotes Treg differentiation and suppresses antitumor immunity
Description	MAP4K family kinases are key kinases for T-cell-mediated immune responses; however, in vivo roles of MAP4K2 in immune regulation remain unclear. Using T-cell-specific Map4k2 conditional knockout (T-Map4k2 cKO) mice, single-cell RNA sequencing (scRNA-seq), and mass spectrometry analysis, we found that MAP4K2 interacted with DDX39B, induced FOXP3 gene expression, and promoted Treg differentiation. Mechanistically, MAP4K2 directly phosphorylated the DEAD box protein DDX39B, leading to DDX39B nuclear translocation and subsequent Foxp3 RNA splicing. MAP4K2-induced FOXP3 mRNA levels were abolished in DDX39B knockout T cells. Furthermore, T-Map4k2 cKO mice displayed the reduction of Treg population and sustained inflammation during remission phase of EAE autoimmune disease model. Remarkably, the anti-PD-1 immunotherapeutic effect on pancreatic cancer was drastically improved in T-Map4k2 cKO mice, Treg-specific Map4k2-deficient mice, adaptively transferred mice, or MAP4K2-inhibitor-treated mice. Consistently, scRNA-seq analysis of human pancreatic patients showed increased MAP4K2 levels in infiltrating Treg cells. Collectively, MAP4K2 promotes Treg differentiation by inducing DDX39B nuclear translocation, leading to the attenuation of tumor immunity.
HostingRepository	PRIDE
AnnounceDate	2025-12-16
AnnouncementXML	Submission_2025-12-15_19:00:43.879.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Huai-Chia Chuang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-19 06:47:32	ID requested
⏵ 1	2025-12-15 19:00:44	announced

Dataset with its publication pending

submitter keyword: MAP4K2, DDX39B, FOXP3, immunotherapy, Treg

Tse-Hua Tan
contact affiliation	Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
contact email	ttan@nhri.edu.tw
lab head
Huai-Chia Chuang
contact affiliation	Immunology Research Center, National Health Research Institutes
contact email	cinth@nhri.org.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070940
     1. Label: PRIDE project
     2. Name: MAP4K2 promotes Treg differentiation and suppresses antitumor immunity