PXD062710
PXD062710 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Noscapine derivative 428 suppresses ferroptosis through targeting GPX4 |
| Description | Inhibiting ferroptosis represents a promising strategy to combat ferroptosis-related diseases. Here we show that 428, a selenide-containing noscapine derivative, effectively inhibits ferroptosis in various cell lines by enhancing the stability and activity of GPX4. TRIM41 was identified as a novel E3 ubiquitin ligase of GPX4 and 428 was demonstrated to bind to the selenocysteine residue Sec46 of GPX4 via the formation of a transient and reversible Se-Se bond, thereby blocking the interaction between GPX4 and TRIM41, stabilizing GPX4 and enhancing its activity. This unique dynamic covalent binding mode was preliminarily validated by structure-activity relationship analysis and molecular docking studies. Importantly, we demonstrated that 428 treatment alleviates bleomycin-induced pulmonary fibrosis in vivo by inhibiting ferroptosis. Overall, our studies identified a novel stabilizer and activator of GPX4, offering a potential therapeutic approach for the treatment of ferroptosis-related diseases and uncovering a new mechanism for regulating GPX4 degradation. |
| HostingRepository | iProX |
| AnnounceDate | 2025-04-08 |
| AnnouncementXML | Submission_2025-04-08_00:21:47.783.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Youping Zhang |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-04-08 00:21:35 | ID requested | |
| ⏵ 1 | 2025-04-08 00:21:48 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Ferroptosis, GPX4, Noscapine derivative, Idiopathic pulmonary fibrosis, Selenocysteine, TRIM41 |
Contact List
| Yingli Wu | |
|---|---|
| contact affiliation | Shanghai jiaotong University |
| contact email | wuyingli@shsmu.edu.cn |
| lab head | |
| Youping Zhang | |
| contact affiliation | Shanghai Jiaotong University |
| contact email | zhangypfj0110@163.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
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