PXD079156

PXD079156 is an original dataset announced via ProteomeXchange.

Title	Enhancing Trim25-ORF1p interaction with a small molecule mitigates LINE-1 ORF1p accumulation in aged germ cells
Description	Retrotransposition of long interspersed nuclear element-1 (LINE-1) drives genomic instability, thereby contributing to congenital malformations and aging. While the transcriptional control of LINE-1 is well-documented, the post-translational regulation of its protein products remains poorly understood. Here we show that the E3 ubiquitin ligase TRIM25 interacts with ORF1p and promotes its degradation through ubiquitination. Exploiting this mechanism and guided by molecular dynamics simulations, we identified a small-molecule compound that cooperatively stabilizes the TRIM25-ORF1p interaction to accelerate target degradation. Given that age-related LINE-1 activation in germ cells contributes to de novo mutations and reproductive risks in older parents, our findings demonstrate a targeted pharmacological approach to downregulate ORF1p. This study provides a framework for mitigating age-associated genomic instability by modulating LINE-1 protein levels.
HostingRepository	iProX
AnnounceDate	2026-06-01
AnnouncementXML	Submission_2026-06-01_19:49:52.852.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wanqian Li
SpeciesList	scientific name: Rattus rattus; NCBI TaxID: 10117;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-01 19:49:10	ID requested
⏵ 1	2026-06-01 19:49:53	announced

Dataset with its publication pending

submitter keyword: LINE-1, TRIM25, ubiquitination, retrotransposition

Feng Li
contact affiliation	Nanjing Medical University
contact email	lifeng@njmu.edu.cn
lab head
Wanqian Li
contact affiliation	Nanjing Medical University
contact email	19565766836@163.com
dataset submitter

iProX dataset URI