{
  "abstract": "Cellular senescence is accompanied 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 identified N-acetylglucosamine-1-phosphotransferase subunits alpha and beta (GNPTAB), an enzyme responsible for lysosomal hydrolase targeting, as a positive regulator of cellular senescence. Genetic ablation of GNPTAB attenuated senescence, whereas its overexpression accelerated senescence. This pro-senescent function occurred independently of GNPTAB’s canonical enzymatic role. Instead, GNPTAB binds to the innate immune adaptor stimulator of interferon genes (STING) through an interface involving the critical residue E1119, leading to activation of STING and its downstream TANK-binding kinase 1 (TBK1), as well as pro-inflammatory gene expression. A STING-binding-deficient GNPTAB mutant (E1119A) preserved canonical lysosomal functions but failed to induce senescence, while STING depletion abolished GNPTAB-driven senescence. Together, these findings uncover a new signaling pathway wherein GNPTAB engages STING to facilitate its activation, suggesting that the GNPTAB-STING interaction interface may serve as a potential therapeutic target for ameliorating age-related cellular dysfunction.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Jian Yin"
    },
    {
      "name": "Yizhou Gao"
    },
    {
      "name": "Yaobin Jing"
    },
    {
      "name": "Xiaoyu Jiang"
    },
    {
      "name": "Feibo Wang"
    },
    {
      "name": "Yusheng Cai"
    },
    {
      "name": "Ming-Heng Li"
    },
    {
      "name": "Tianling Cao"
    },
    {
      "name": "Min Wang"
    },
    {
      "name": "Yifang He"
    },
    {
      "name": "Hongkai Zhao"
    },
    {
      "name": "Sheng Zhang"
    },
    {
      "name": "Shuai Ma"
    },
    {
      "name": "Si Wang"
    },
    {
      "name": "Guang-Hui Liu",
      "orcid": "0000-0001-9289-8177"
    },
    {
      "name": "Weiqi Zhang",
      "orcid": "0000-0002-8885-5104"
    },
    {
      "name": "Jing Qu",
      "orcid": "0000-0002-3988-5067"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7gkc9fd7fzg5r.bib",
  "cited_by": 0,
  "doi": "10.1093/procel/pwag049",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13721126/",
  "id": "7gkc9fd7fzg5r",
  "issns": [
    "1674-800X",
    "1674-8018"
  ],
  "landing_url": "https://doi.org/10.1093/procel/pwag049",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI00960"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2737|Telomeres, Telomerase, and Senescence"
    ]
  ],
  "openalex": "W7171472265",
  "pdf_url": null,
  "pmcid": "PMC13721126",
  "pmid": "42505080",
  "published": "2026-07-27",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/7gkc9fd7fzg5r.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:52Z",
      "native_id": "PMC13721126",
      "source": "pmc",
      "url": "https://doi.org/10.1093/procel/pwag049"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Telomeres, Telomerase, and Senescence",
      "subfield": "physiology"
    }
  ],
  "title": "CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence",
  "title_text": "CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:52Z",
  "url": "https://research.draconitic.com/paper/7gkc9fd7fzg5r",
  "venue": "Protein & Cell",
  "versions": []
}