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PXD073745-1
PXD073745 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | ARIH1 mediates PRDX4 ubiquitination |
| Description | Ferroptosis offers a promising therapeutic vulnerability in triple-negative breast cancer (TNBC), yet resistance limits efficacy in the predominant basal-like subtype. Here, we demonstrate that peroxiredoxin 4 (PRDX4) is a key regulator of this ferroptosis resistance. Functionally, PRDX4 suppresses ferroptosis by inhibiting lipid peroxidation in the endoplasmic reticulum (ER) and reducing the formation of mitochondria-associated membranes (MAMs), thereby blocking interorganellar lipid and calcium transfer. Mechanistically, PRDX4 dimers competitively bind the substrate-binding domain of GRP75, impeding the assembly of the IP3R3-GRP75-VDAC1 complex. Notably, this inhibitory function relies on protein-protein interactions rather than its conserved peroxidase activity. Therapeutically, targeted PRDX4 degradation via the E3 ubiquitin ligase ARIH1 or the small molecule compound TLC69 effectively induces ferroptosis and suppresses tumor growth in vivo. Collectively, our study reveals the role of PRDX4 as a ferroptosis suppressor, delineates a PRDX4-GRP75-MAMs regulatory axis, and provides a potential targeting strategy to sensitize TNBC to ferroptosis. |
| HostingRepository | iProX |
| AnnounceDate | 2026-01-29 |
| AnnouncementXML | Submission_2026-01-28_19:06:57.152.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Bing Shan |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | ubiquitination signature dipeptidyl lysine |
| Instrument | timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-01-28 19:06:42 | ID requested | |
| ⏵ 1 | 2026-01-28 19:06:57 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: PRDX4 ubiquitination |
Contact List
| Yaoyang Zhang | |
|---|---|
| contact affiliation | Shanghai institute of Organic Chemistry, Chinese Academy of Sciences |
| contact email | zyy@sioc.ac.cn |
| lab head | |
| Bing Shan | |
| contact affiliation | Shanghai institute of Organic Chemistry,Chinese Academy of Sciences |
| contact email | shanbing@sioc.ac.cn |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
