{
  "abstract": "Ubiquitination is an important posttranslational modification associated with essential cellular processes. Here we show that deletion of E3 ubiquitin ligase HECTD3 — germline or in hematopoietic compartment, including in Cd11c+ cells — causes severe disease and increased production of proinflammatory cytokines in a murine model of ulcerative colitis (UC). HECTD3 mRNA levels were found reduced in colonic tissues of patients with UC, which highlights a potential role for HECTD3 in regulating inflammatory responses in UC. We identified MyD88, a central adaptor in the TLR/IL-1R signaling and inflammatory response, as a target for HECTD3 ubiquitination. We demonstrate that HECTD3 ubiquitinates MyD88 through K27-linked Poly-Ub chains in a nondegradative manner. HECTD3-KO GM-CSF–bone marrow–derived cells treated with the TLR4 ligand LPS produced more proinflammatory cytokines, showed elevated phosphorylation of NF-κB and IRAK4, as well as increased association of MyD88 with IRAK4, demonstrating that HECTD3 controls MyD88/IRAK4/NF-κB axis. Inhibition of MyD88 activity rescued colitis severity in the HECTD3-KO mice, including the elevated proinflammatory cytokine production. Thus, our results establish MyD88 as a target for HECTD3 nondegradative polyubiquitination and restriction of innate immune colonic inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.",
    "Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USA.",
    "Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.",
    "J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA.",
    "Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, Department of Chemistry and Biochemistry, College of Science & College of Medicine, The BIO5 Institute, The University of Arizona, Tucson, Arizona, USA.",
    "Taplin Mass Spectrometry Facility, Harvard Medical School, Boston, Massachusetts, USA.",
    "Department of Pharmacology and Therapeutics and",
    "Department of Microbiology and Cell Science, IFAS, University of Florida, Gainesville, Florida, USA.",
    "Department of Pathology, NYU School of Medicine, New York, New York, USA.",
    "Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA.",
    "Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.",
    "Department of Biochemistry & Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 31,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shamima Islam"
    },
    {
      "affs": [
        0
      ],
      "name": "Shahnewaj Mannan"
    },
    {
      "affs": [
        1
      ],
      "name": "Ashley Zuniga"
    },
    {
      "affs": [
        1
      ],
      "name": "Upasana Parthasarathy"
    },
    {
      "affs": [
        0
      ],
      "name": "Valeriu B. Cismasiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Leonardo Silvane"
    },
    {
      "affs": [
        0
      ],
      "name": "Sayan Chakraborty"
    },
    {
      "affs": [
        0
      ],
      "name": "Divya Priyanka Talada"
    },
    {
      "affs": [
        0
      ],
      "name": "Raghwendra Pratap Singh"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomas Zelenka"
    },
    {
      "affs": [
        0
      ],
      "name": "Amreen Naveen"
    },
    {
      "affs": [
        0
      ],
      "name": "Sephra Chyanne Vickers"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael G.M. Grant"
    },
    {
      "affs": [
        1
      ],
      "name": "Jonathan J. Cho"
    },
    {
      "affs": [
        1
      ],
      "name": "Theodore Drashansky"
    },
    {
      "affs": [
        3
      ],
      "name": "Alexander J. Kwiatkowski"
    },
    {
      "affs": [
        4
      ],
      "name": "Xintong Liu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ross Tomaino"
    },
    {
      "affs": [
        6
      ],
      "name": "Olga A. Guryanova"
    },
    {
      "affs": [
        7
      ],
      "name": "Mariola J. Ferraro"
    },
    {
      "affs": [
        8
      ],
      "name": "Sang Yong Kim"
    },
    {
      "affs": [
        9
      ],
      "name": "Christian Jobin",
      "orcid": "0000-0002-3733-1001"
    },
    {
      "affs": [
        3
      ],
      "name": "Benjamin G. Keselowsky"
    },
    {
      "affs": [
        4
      ],
      "name": "Hongmin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Paulo C. Rodriguez",
      "orcid": "0000-0001-7480-6566"
    },
    {
      "affs": [
        0
      ],
      "name": "Martina Molgora"
    },
    {
      "affs": [
        0
      ],
      "name": "Amer A. Beg"
    },
    {
      "affs": [
        10
      ],
      "name": "Timothy I. Shaw",
      "orcid": "0000-0002-9316-1924"
    },
    {
      "affs": [
        11
      ],
      "name": "Zheng Ruan"
    },
    {
      "affs": [
        2
      ],
      "name": "Lixin Wan",
      "orcid": "0000-0002-9759-5113"
    },
    {
      "affs": [
        0
      ],
      "name": "Dorina Avram"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7t49ggdz52apf.bib",
  "cited_by": 0,
  "doi": "10.1172/jci.insight.185437",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726568/",
  "id": "7t49ggdz52apf",
  "issns": [
    "2379-3708"
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  "landing_url": "https://doi.org/10.1172/jci.insight.185437",
  "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",
      "Research Article"
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      "openalex",
      "2403|Immune Response and Inflammation"
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  "openalex": "W7214233337",
  "pdf_url": "http://insight.jci.org/articles/view/185437/files/pdf",
  "pmcid": "PMC13726568",
  "pmid": "42784256",
  "published": "2026-09-24",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/7t49ggdz52apf.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:52Z",
      "native_id": "PMC13726568",
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      "url": "https://doi.org/10.1172/jci.insight.185437"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Response and Inflammation",
      "subfield": "immunology"
    }
  ],
  "title": "The E3 ubiquitin ligase HECTD3 controls immune colonic inflammation by restricting MyD88 activation and signaling",
  "title_text": "The E3 ubiquitin ligase HECTD3 controls immune colonic inflammation by restricting MyD88 activation and signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:29Z",
  "url": "https://research.draconitic.com/paper/7t49ggdz52apf",
  "venue": "JCI Insight",
  "versions": []
}