{
  "abstract": "gene, encoding a deubiquitinase with exclusive specificity for linear ubiquitin chains, cause a severe multiorgan autoinflammatory condition involving the skin. Mice lacking OTULIN selectively in keratinocytes develop inflamed skin lesions that progress into squamous tumors, a phenotype driven by excessive tumor necrosis factor (TNF)-induced cell death. Previous studies suggest a role for OTULIN in mediating Wnt signaling during development, but the physiological relevance of this association is unknown. Here, we show that OTULIN promotes Wnt signaling in keratinocytes by regulating the linear ubiquitination status of β-catenin. Stabilization of β-catenin in OTULIN-deficient keratinocytes prevents progressive skin inflammation in prophylactic and therapeutic settings by blocking keratinocyte death. We demonstrate that OTULIN prevents proteasomal degradation of β-catenin in cultured keratinocytes. Reduced Wnt signaling in OTULIN-deficient keratinocytes leads to degradation of TCF3/4, an essential survival factor for keratinocytes. Collectively, our data identify OTULIN's linear deubiquitination activity as a key regulator of epithelial cell viability, not only by preventing cell death downstream of TNF, but also by promoting canonical Wnt signaling.",
  "abstract_shown": true,
  "affiliations": [
    "VIB Center for Inflammation Research, 9052 Ghent, Belgium.",
    "Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.",
    "Cancer Research Institute Ghent (CRIG), Ghent, Belgium."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kim Lecomte",
      "orcid": "0000-0001-8402-9799"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Pieter Hertens",
      "orcid": "0000-0002-8994-5224"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Virginie Wylleman",
      "orcid": "0009-0006-6445-3000"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Annagiada Toniolo",
      "orcid": "0000-0001-6332-6225"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Febe Roelandt",
      "orcid": "0009-0002-8354-5999"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Fleur Boone",
      "orcid": "0000-0002-6492-8401"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Maarten Ciers"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lien Verboom",
      "orcid": "0000-0002-1942-4554"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Katrien Staes",
      "orcid": "0009-0004-2343-8686"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Geert van Loo",
      "orcid": "0000-0002-8427-4775"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Esther Hoste",
      "orcid": "0000-0002-3181-431X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/57q4dvgb66b2q.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.adz0181",
  "fulltext_url": null,
  "id": "57q4dvgb66b2q",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.adz0181",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Wnt/β-catenin signaling in development and cancer"
    ]
  ],
  "openalex": "W7221159741",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/57q4dvgb66b2q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.adz0181",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.adz0181"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Wnt/β-catenin signaling in development and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Canonical Wnt induction by OTULIN prevents keratinocyte death and skin inflammation",
  "title_text": "Canonical Wnt induction by OTULIN prevents keratinocyte death and skin inflammation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/57q4dvgb66b2q",
  "venue": "Science Advances",
  "versions": []
}