PXD066377

PXD066377 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-21 20:28:07	ID requested
⏵ 1	2025-07-21 20:28:23	announced

Dataset with its publication pending

submitter keyword: Auranofin, TOPBP1, breast cancer

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

iProX dataset URI