{
  "abstract": "Aberrant activation of the Sonic Hedgehog (SHH)-glioma-associated oncogene 1 (GLI1) signaling pathway is a determinant driver of basal cell carcinoma (BCC) and SHH-subgroup medulloblastoma (MBSHH). Here, we demonstrate the role of S-palmitoylation and depalmitoylation of GLI1 in the regulation of incidence and progression of MBSHH. High expression of acyltransferase ZDHHC13 in MBSHH induces S-palmitoylation of human GLI1 at Cys1034, stabilizes GLI1 by preventing its ubiquitin-dependent proteasomal degradation, and in turn activates this signaling pathway to promote the progression of MBSHH. Conversely, the deacylase ABHD17A depalmitoylates GLI1 at Cys1034, destabilizes GLI1, and in turn inactivates this signaling pathway. As a result, conditional knockout of Zdhhc13 in cerebellar granule neuron precursors (GNPs) significantly alleviates the severity of MBSHH induced by constitutively active Smoothened (Smo-M2) overexpression and markedly extends overall survival, whereas knockout of Abhd17a increases the incidence of MBSHH induced by Patched-1 ablation, rather than its progression. Together, these findings uncover the dynamic regulation of GLI1 palmitoylation and depalmitoylation by the ZDHHC13 and ABHD17A and subsequent GLI1 stabilization and destabilization as a hitherto uncharacterized mechanism controlling SHH/GLI1 signaling and may provide additional targets for therapeutic intervention of MBSHH.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology, Zhejiang University School of Medicine",
    "Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital",
    "Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Hangzhou City University School of Medicine",
    "National Clinical Research Center for Child Health, The Children’s Hospital of Zhejiang University School of Medicine",
    "Shulan International Medical College, Zhejiang Shuren University",
    "Department of Pharmacy, Hangzhou First People’s Hospital Affiliated of Westlake University School of Medicine",
    "College of Pharmaceutical Sciences, Zhejiang University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tingyu Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Hangyang Bao"
    },
    {
      "affs": [
        1
      ],
      "name": "Jirong Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Xing Ji"
    },
    {
      "affs": [
        3
      ],
      "name": "Weizhong Gu"
    },
    {
      "affs": [
        3
      ],
      "name": "Chao Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiangqiang He"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiahao Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Tan"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiali Yao"
    },
    {
      "affs": [
        2
      ],
      "name": "Chengyun Xu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ying Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Ximei Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shi-Hong Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Ling-Hui Zeng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ce5bryy4ajbj2.bib",
  "cited_by": 1,
  "doi": "10.1038/s41419-026-09051-y",
  "fulltext_url": "https://doi.org/10.1038/s41419-026-09051-y",
  "id": "ce5bryy4ajbj2",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://doi.org/10.1038/s41419-026-09051-y",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH573-671"
    ],
    [
      "openalex",
      "1312|Hedgehog Signaling Pathway Studies"
    ]
  ],
  "openalex": "W7166537977",
  "pdf_url": "https://www.nature.com/articles/s41419-026-09051-y_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/ce5bryy4ajbj2.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T14:21:03Z",
      "native_id": "0de97cd7cb9e4b2795977bdb12b15915",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41419-026-09051-y"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Hedgehog Signaling Pathway Studies",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Dynamic S-palmitoylation of glioma-associated oncogene 1 regulates the incidence and progression of Sonic Hedgehog medulloblastoma",
  "title_text": "Dynamic S-palmitoylation of glioma-associated oncogene 1 regulates the incidence and progression of Sonic Hedgehog medulloblastoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T14:21:23Z",
  "url": "https://research.draconitic.com/paper/ce5bryy4ajbj2",
  "venue": "Cell Death and Disease",
  "versions": []
}