PXD048953

PXD048953 is an original dataset announced via ProteomeXchange.

Title	Identification of a Novel Ferroptosis Inducer with Dual Modulatory Effects on GPX4 Activity and Stability
Description	Ferroptosis is a unique form of intracellular iron-dependent cell death that differs from apoptosis, necrosis, and autophagy. GPX4, an antioxidant defense enzyme, plays a pivotal role as regulator of ferroptosis. Extensive researches suggest that targeting GPX4 holds promise for cancer therapy. However, the current GPX4 inhibitors face challenges due to unfavorable drug-like properties, which hinder their progress in clinical development. In this study, we identified a novel inhibitor called MI-2, demonstrating potent ferroptosis-inducing capacity. Mechanistically, MI-2 effectively inhibits the activity of GPX4 by direct interaction. Furthermore, MI-2 promotes the degradation of GPX4 through its well-established target, MALT1. In multiple cancer models, MI-2 has demonstrated synergistic effects when combined with sorafenib or regorafenib, resulting in enhanced ferroptosis induction. These findings highlight the dual modulatory effects of MI-2 on GPX4 activity and stability, offering a promising starting point for the development of drug-like GPX4 inhibitors with translational potential.
HostingRepository	iProX
AnnounceDate	2024-01-27
AnnouncementXML	Submission_2024-04-22_18:48:06.202.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bo Yang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-28 20:16:13	ID requested
⏵ 1	2024-04-22 18:48:06	announced

Dataset with its publication pending

submitter keyword: Ferroptosis, MI-2, GPX4

Cun Wang
contact affiliation	Shanghai Jiao Tong University
contact email	cwang@shsci.org
lab head
Bo Yang
contact affiliation	East China Normal University
contact email	yangbo6674@163.com
dataset submitter

iProX dataset URI