PXD064117

PXD064117 is an original dataset announced via ProteomeXchange.

Title	A ROS-mediated Oxidation-O-GlcNAcylation cascade governs ferroptosis
Description	Reactive oxygen species (ROS) play a crucial role in lipid peroxidation and the initiation of ferroptosis, significantly affecting chemotherapeutic drug resistance. However, the mechanisms by which ROS function and are sensed remain poorly understood. In this study, we identified O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, as a sensor for ROS induced by ferroptosis. The ROS-induced oxidation of OGT at C845 in its catalytic domain activates the enzyme. Once activated, OGT O-GlcNAcylates FOXK2, enhancing its interaction with importin α, which facilitates FOXK2's nuclear translocation and binding to the SLC7A11 promoter region. This, in turn, boosts SLC7A11 transcription, thereby inhibiting ferroptosis. The elevated OGT-FOXK2-SLC7A11 axis contributes to tumorigenesis and resistance to chemoradiotherapy in hepatocellular carcinoma (HCC). Our findings elucidate a ROS-induced oxidation-O-GlcNAcylation cascade that integrates ROS signaling, O-GlcNAcylation, FOXK2-mediated SLC7A11 transcription, and resistance to both ferroptosis and chemoradiotherapy.
HostingRepository	PRIDE
AnnounceDate	2025-05-28
AnnouncementXML	Submission_2025-05-28_08:29:21.381.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064117
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Chunyan Hou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; N-acetylaminohexosylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-20 10:15:11	ID requested
⏵ 1	2025-05-28 08:29:21	announced

10.6019/PXD064117;

submitter keyword: Human, OGT, FOXK2, LC-MS/MS

Junfeng Ma
contact affiliation	Georgetown University Medical Center
contact email	junfeng.Ma@georgetown.edu
lab head
Chunyan Hou
contact affiliation	Georgetown University
contact email	ch1363@georgetown.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064117
     1. Label: PRIDE project
     2. Name: A ROS-mediated Oxidation-O-GlcNAcylation cascade governs ferroptosis