{
  "abstract": "TGF-β signaling plays a pivotal role in regulating numerous cellular processes, primarily through the Smad-dependent pathway. Disruptions of the pathway are associated with developmental disorders and life-threatening diseases, such as cancer. It has been reported that TRIM33 inactivates Smad4 signaling and also drives its own signaling responses. However, the mechanism controlling TRIM33 activity has remained unclear. In this study, we identify DCAF6 as a previously unrecognized ubiquitin ligase for TRIM33. DCAF6 targets TRIM33 at Lys850 for ubiquitin-dependent proteasomal degradation, thus abolishing TRIM33-mediated mono-ubiquitination of Smad4. As such, DCAF6 induces dual consequences: it enhances Smad4-dependent transcriptional and growth inhibitory responses, while simultaneously eliminating TRIM33-dependent developmental responses. Conversely, DCAF6 knockout suppresses Smad4-dependent responses while amplifying TRIM33-dependent responses. Therefore, DCAF6 operates as a critical regulator in the balance of TGF-β signaling between the Smad4 and TRIM33 pathways. These insights deepen our understanding of the dynamics and fate control of TGF-β signaling and may open avenues for therapeutic approaches targeting TGF-β in diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Ministry of Education Key Laboratory of Biosystems Homeostasis and Protection and Zhejiang Key Laboratory of Molecular Cancer Biology, Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, Zhejiang, China",
    "Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing 321000, Zhejiang, China",
    "Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China",
    "Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China",
    "Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala 751 23, Sweden",
    "The Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, Zhejiang, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hongjie Luo",
      "orcid": "0000-0002-4036-7881"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Bo Yuan"
    },
    {
      "affs": [
        3
      ],
      "name": "Jinquan Liu"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Zeda Yao",
      "orcid": "0009-0007-2514-8457"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Huanyu Hong",
      "orcid": "0009-0008-7955-4511"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Dachuan Lin"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Shuyi Zhang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jiayi Qian"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jie Li"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jin Cao"
    },
    {
      "affs": [
        3
      ],
      "name": "Xia Lin"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bin Zhao",
      "orcid": "0000-0002-1690-646X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Pinglong Xu",
      "orcid": "0000-0001-7726-5443"
    },
    {
      "affs": [
        4
      ],
      "name": "Carl-Henrik Heldin",
      "orcid": "0000-0002-9508-896X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jianping Jin",
      "orcid": "0000-0003-2722-0591"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yi Yu"
    },
    {
      "affs": [
        0,
        1,
        2,
        5
      ],
      "name": "Xin-Hua Feng",
      "orcid": "0000-0002-4418-0811"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bbmv5krrxfv6z.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2602333123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732256/",
  "id": "bbmv5krrxfv6z",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2602333123",
  "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",
      "409"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "openalex",
      "1312|TGF-β signaling in diseases"
    ]
  ],
  "openalex": "W7224092349",
  "pdf_url": null,
  "pmcid": "PMC13732256",
  "pmid": "42949977",
  "published": "2026-10-28",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/bbmv5krrxfv6z.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:16Z",
      "native_id": "PMC13732256",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2602333123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell Biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "DCAF6 reprograms TGF-β responses through TRIM33 destruction",
  "title_text": "DCAF6 reprograms TGF-β responses through TRIM33 destruction",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:16Z",
  "url": "https://research.draconitic.com/paper/bbmv5krrxfv6z",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}