⮝ Full datasets listing
PXD066377-1
PXD066377 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Auranofin improves chemotherapeutic response of breast tumor by targeting TOPBP1-nucleated protein complexes |
| Description | Genome instability is most commonly caused by replication stress, which also renders cancer cells extremely vulnerable once their response to replication stress is impeded. Topoisomerase II binding protein 1 (TOPBP1), an allosteric activator of ataxia telangiectasia and Rad3 related (ATR) kinase, coordinates ATR in replication stress response and has emerged as a potential therapeutic target for tumors. Here, we identify auranofin, the FDA-approved drug for rheumatoid arthritis, as a lead compound capable of binding to the BRCT 7-8 domains and blocking TOPBP1 interaction with PHF8 and FANCJ. The liquid-liquid phase separation (LLPS) of TOPBP1 was also disrupted by auranofin. Through targeting these TOPBP1-nucleated molecular machineries, auranofin leads to an accumulation of replication defects by impairing ATR activation and attenuating RPA loading on perturbed replication forks, and it shows significant anti-breast tumor activity in combination with PARP inhibitor (PARPi). This study provides mechanistic insights into how auranofin challenges replication integrity and expands the application of this FDA-approved drug in breast tumor intervention. |
| HostingRepository | iProX |
| AnnounceDate | 2025-07-21 |
| AnnouncementXML | Submission_2025-07-21_20:28:23.072.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Shuai Ma |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-07-21 20:28:07 | ID requested | |
| ⏵ 1 | 2025-07-21 20:28:23 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Auranofin, TOPBP1, breast cancer |
Contact List
| Lei Shi | |
|---|---|
| contact affiliation | Tianjin Medical University |
| contact email | shilei@tmu.edu.cn |
| lab head | |
| Shuai Ma | |
| contact affiliation | Tianjin Medical University |
| contact email | yjs_mashuai@tmu.edu.cn |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
