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PXD073027

PXD073027 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence
DescriptionCellular senescence is characterized by profound lysosomal alterations, yet whether lysosome-associated factors actively drive aging remains unclear. Through a focused CRISPR/Cas9 screen in human mesenchymal progenitor cells (hMPCs), we identify GNPTAB, an enzyme for lysosomal hydrolase targeting, as a potent regulator of senescence. Genetic ablation of GNPTAB attenuated senescence, while its overexpression accelerated aging. Notably, this pro-senescent function was independent of GNPTAB’s canonical enzymatic role. Mechanistically, GNPTAB binds to the innate immune adaptor STING via a specific interface (E1119), triggering downstream TBK1 activation and inflammatory gene expression. A STING-binding-deficient GNPTAB mutant (E1119A) retained enzymatic function but failed to induce senescence, and STING depletion abolished GNPTAB-driven senescence. Our work defines a non-canonical, lysosome-to-immune signaling pathway wherein GNPTAB acts as a direct STING activator, nominating this interface as a candidate target for mitigating age-related cellular dysfunction.
HostingRepositoryiProX
AnnounceDate2026-01-11
AnnouncementXMLSubmission_2026-01-13_17:53:31.649.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYizhou Gao
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-01-13 17:53:18ID requested
12026-01-13 17:53:32announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: CRISPR screening, aging, cellular senescence, lysosomal biology
Contact List
Jing Qu
contact affiliationInstitute of Zoology, Chinese Academy of Sciences
contact emailqujing@ioz.ac.cn
lab head
Yizhou Gao
contact affiliationInstitute of Zoology, Chinese Academy of Sciences
contact email2412676398@qq.com
dataset submitter
Full Dataset Link List
iProX dataset URI