{
  "abstract": "Gasdermin D (GSDMD), a key pyroptosis effector downstream of inflammasome activation, undergoes precise regulation by multiple posttranslational modifications. Here, we identify SMYD3, a lysine methyltransferase, as a positive regulator of GSDMD. SMYD3 interacts with GSDMD and catalyzes its dimethylation at lysine 43. This modification promotes GSDMD cleavage by caspases, leading to increased oligomerization and membrane localization of GSDMD N-terminal fragment (GSDMD-NT), which ultimately induces pyroptosis. Disrupting or inhibiting SMYD3 alleviates overactivated inflammation, thereby protecting against lipopolysaccharide-induced death in mice and zebrafish. Our findings reveal a role for SMYD3 in regulating the inflammatory response and shed light on a new mechanism that modulates GSDMD-mediated pyroptosis.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People’s Republic of China",
    "Hubei Hongshan Laboratory, Wuhan 430070, People’s Republic of China",
    "Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, People’s Republic of China",
    "University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Zixuan Wang",
      "orcid": "0009-0007-8289-1538"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Shuke Jia"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yiman Luo"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Wen Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoli Zeng",
      "orcid": "0000-0001-7616-0535"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yuhan Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lele Yu",
      "orcid": "0009-0001-4445-8000"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hongyan Deng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xueyi Sun"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Chunchun Zhu"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Wuhan Xiao",
      "orcid": "0000-0002-2978-0616"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Xing Liu",
      "orcid": "0000-0001-9338-7440"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5gph6nd2xp4qd.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2616180123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732053/",
  "id": "5gph6nd2xp4qd",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2616180123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "420"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Immunology and Inflammation"
    ],
    [
      "openalex",
      "1312|Inflammasome and immune disorders"
    ]
  ],
  "openalex": "W7223817199",
  "pdf_url": null,
  "pmcid": "PMC13732053",
  "pmid": "42945245",
  "published": "2026-10-27",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/5gph6nd2xp4qd.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:06Z",
      "native_id": "PMC13732053",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2616180123"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Inflammasome and immune disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "SMYD3-catalyzed dimethylation of gasdermin D at lysine 43 promotes pyroptosis and inflammatory responses",
  "title_text": "SMYD3-catalyzed dimethylation of gasdermin D at lysine 43 promotes pyroptosis and inflammatory responses",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:06Z",
  "url": "https://research.draconitic.com/paper/5gph6nd2xp4qd",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}