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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

NEDD4-1: from molecular mechanisms to clinical translation in human diseases

  • Haifen Tian1
  • Yongsheng Huang2
  • Yun Liang3
  • Chengjun Huang1
  • Bingbing Wei1
  • Chang-Neng Liao1
  • Weijie Zhou4
4 affiliations
  1. 1Department of Pharmacy, Baise People’s Hospital, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Baise, China
  2. 2Department of Neurosurgery, Baise People’s Hospital, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Baise, China
  3. 3Department of Neurology, Baise People’s Hospital, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Baise, China
  4. 4Department of Laboratory, Baise People’s Hospital, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Baise, China
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Abstract

Neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1), the founding member of the HECT family of E3 ubiquitin ligases, mediates substrate protein ubiquitination through its C2, WW, and HECT domains. It plays a key role in protein degradation via both the ubiquitin-proteasome system (UPS) and the lysosomal pathway. Recent evidence highlights the complexity of NEDD4-1’s functions. This review synthesizes advancements in the regulatory mechanisms of NEDD4-1, emphasizing its critical involvement in cancer initiation and progression. Beyond oncology, it highlights NEDD4-1’s vital functions in maintaining nervous system integrity, metabolic balance, cardiovascular health, and immune regulation. By examining the structural features, physiological roles, expression profiles in various diseases, molecular regulatory networks, and potential clinical applications of NEDD4-1, this review provides a comprehensive framework for understanding its biological mechanisms and advancing targeted therapeutic strategies.

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Cite

BibTeXRIS
BibTeX
@article{tian2026nedd41,
  title = {{NEDD4-1: from molecular mechanisms to clinical translation in human diseases}},
  author = {Haifen Tian and Yongsheng Huang and Yun Liang and Chengjun Huang and Bingbing Wei and Chang-Neng Liao and Weijie Zhou},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1897001},
  url = {https://doi.org/10.3389/fphar.2026.1897001},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - NEDD4-1: from molecular mechanisms to clinical translation in human diseases
AU  - Haifen Tian
AU  - Yongsheng Huang
AU  - Yun Liang
AU  - Chengjun Huang
AU  - Bingbing Wei
AU  - Chang-Neng Liao
AU  - Weijie Zhou
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1897001
UR  - https://doi.org/10.3389/fphar.2026.1897001
AB  - Neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1), the founding member of the HECT family of E3 ubiquitin ligases, mediates substrate protein ubiquitination through its C2, WW, and HECT domains. It plays a key role in protein degradation via both the ubiquitin-proteasome system (UPS) and the lysosomal pathway. Recent evidence highlights the complexity of NEDD4-1’s functions. This review synthesizes advancements in the regulatory mechanisms of NEDD4-1, emphasizing its critical involvement in cancer initiation and progression. Beyond oncology, it highlights NEDD4-1’s vital functions in maintaining nervous system integrity, metabolic balance, cardiovascular health, and immune regulation. By examining the structural features, physiological roles, expression profiles in various diseases, molecular regulatory networks, and potential clinical applications of NEDD4-1, this review provides a comprehensive framework for understanding its biological mechanisms and advancing targeted therapeutic strategies.
SN  - 1663-9812
ER  -