PXD045137

PXD045137 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcylation of YTHDF2 antagonizes ERK-dependent phosphorylation and inhibits lung carcinoma
Description	The intracellular O-linked N-acetylglucosamine (O-GlcNAc) glycosylation mediates many signal transduction events and regulates tumorigenesis. Previously the RNA N6-methyladenosine (m6A) reader, YTH (YT521-B homology) domain 2 (YTHDF2), has been shown to be O-GlcNAcylated on Ser-263 during Hepatitis B virus (HBV) infection and promote HBV-related hepatocellular carcinoma. Herein we mapped YTHDF2 O-GlcNAcylation at Thr-49 via electron-transfer dissociation mass spectrometry under unperturbed conditions. We show that YTHDF2 Thr-49 O-GlcNAcylation antagonizes Extracellular-signal regulated kinase (ERK)-dependent phosphorylation at Ser-39 and promotes YTHDF2 degradation. The downstream signaling pathway of YTHDF2 in lung carcinoma are thus upregulated, which leads to the downregulation of c-Myc. We further used mouse xenograft models to show that YTHDF2-T49A mutants increased lung cancer mass and size. Our work reveals a key role of YTHDF2 O-GlcNAcylation in tumorigenesis and suggests that O-GlcNAcylation exerts distinct functions under different biological stress.
HostingRepository	PRIDE
AnnounceDate	2026-02-09
AnnouncementXML	Submission_2026-02-08_16:06:09.724.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045137
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Wen Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-06 00:43:00	ID requested
⏵ 1	2026-02-08 16:06:10	announced

10.6019/PXD045137;

10.1016/j.fmre.2024.07.003;

Li J, Zhou W, Zhang J, Ma L, Lv Z, Geng Y, Chen X, Li J, O-GlcNAcylation of YTHDF2 antagonizes ERK-dependent phosphorylation and inhibits lung carcinoma. Fundam Res, 5(5):2388-2396(2025) [pubmed]

submitter keyword: O-GlcNAc

m6A

c-Myc

ERK

lung carcinoma

Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
lab head
Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045137
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation of YTHDF2 antagonizes ERK-dependent phosphorylation and inhibits lung carcinoma