{
  "abstract": "Parkin is an E3 ubiquitin ligase and its function is primarily regulated by its phosphorylation, yet the role of Parkin ubiquitination remains unclear. Here, we identified the Parkin ubiquitination site at lysine 27 (K27) by mass spectrometry. CHX chase assay confirmed that Parkin ubiquitination-deficient mutant (K27R) exhibited the reduction of Parkin stability. Meanwhile, USP10 was validated as a deubiquitinating enzyme regulating Parkin. Importantly, the Parkin mutant also showed the impaired mitochondrial translocation and the diminished interaction with PINK1, indicating the decreased Parkin phosphorylation. Reciprocally, the Parkin phosphorylation-deficient mutant (S65A) reduced the Parkin ubiquitination level, revealing an interplay between Parkin ubiquitination and its phosphorylation. Functionally, the Parkin mutant elevated the levels of mitochondrial membrane proteins, indicating the impaired mitophagy, which subsequently triggered the release of mitochondrial DNA (mtDNA) and the activation of the cGAS‑STING pathway. Moreover, the Parkin mutant suppressed the oxidative phosphorylation while it markedly enhanced the intracellular glycolysis. Finally, the Parkin mutant promoted the tumor spheroid formation and accelerated tumor growth in vivo, demonstrating the loss of its tumor-suppressive function. Collectively, our findings revealed that Parkin ubiquitination governs its stability and its function in cervical cancer, and may serve as a potential biomarker and therapeutic target.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06362-3.",
  "abstract_shown": true,
  "affiliations": [
    "The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053 Zhejiang China",
    "Department of Medical Oncology, Cancer Center, Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, 310014 Zhejiang China",
    "The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370 Guangdong China",
    "Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, 510370 Guangdong China",
    "Department of Clinical Laboratory, Yuhuan City People’s Hospital, Taizhou, 318000 Zhejiang China",
    "Department of Gynecology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, 310014 Zhejiang China",
    "General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, 310014 Zhejiang China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuanyuan Mai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hui Hua"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Shicong Liang"
    },
    {
      "affs": [
        4
      ],
      "name": "Guiqin Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Sangni Qian"
    },
    {
      "affs": [
        1
      ],
      "name": "Zixuan Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Wenjie Zeng"
    },
    {
      "affs": [
        5
      ],
      "name": "Xiaoyan Chen"
    },
    {
      "affs": [
        6
      ],
      "name": "Qinghui Zheng"
    },
    {
      "affs": [
        5
      ],
      "name": "Huafeng Shou"
    },
    {
      "affs": [
        1
      ],
      "name": "Jianbin Zhang",
      "orcid": "0009-0009-2639-7812"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c24ew7992cr11.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06362-3",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696628/",
  "id": "c24ew7992cr11",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://doi.org/10.1007/s00018-026-06362-3",
  "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",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Ubiquitin and proteasome pathways"
    ]
  ],
  "openalex": "W7204175190",
  "pdf_url": "https://europepmc.org/articles/PMC13696628?pdf=render",
  "pmcid": "PMC13696628",
  "pmid": "42928378",
  "published": "2026-08-26",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/c24ew7992cr11.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:57Z",
      "native_id": "PMC13696628",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00018-026-06362-3"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928378",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928378"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ubiquitin and proteasome pathways",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Ubiquitination of parkin influences its tumor suppressive function in cervical cancer",
  "title_text": "Ubiquitination of parkin influences its tumor suppressive function in cervical cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:56Z",
  "url": "https://research.draconitic.com/paper/c24ew7992cr11",
  "venue": "Cellular and Molecular Life Sciences: CMLS",
  "versions": []
}