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PXD048953

PXD048953 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of a Novel Ferroptosis Inducer with Dual Modulatory Effects on GPX4 Activity and Stability
DescriptionFerroptosis 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.
HostingRepositoryiProX
AnnounceDate2024-01-27
AnnouncementXMLSubmission_2024-04-22_18:48:06.202.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBo Yang
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-28 20:16:13ID requested
12024-04-22 18:48:06announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Ferroptosis, MI-2, GPX4
Contact List
Cun Wang
contact affiliationShanghai Jiao Tong University
contact emailcwang@shsci.org
lab head
Bo Yang
contact affiliationEast China Normal University
contact emailyangbo6674@163.com
dataset submitter
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