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Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and

Na Deng1,2, Qiang Sun3,4, Xue Yu4

  • 1Key Laboratory of Molecular Pathology and Epidemiology of Gastric Cancer in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, Liaoning, China.

Cell Death & Disease
|January 15, 2026
PubMed

Insights

Neddylation, a protein modification, is crucial for cancer development and progression. Targeting this process offers new therapeutic strategies for cancer treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Neddylation is a vital post-translational modification regulating protein stability, function, and localization.
  • This process is essential for tumorigenicity and cancer hallmarks.
  • Cellular stress, including hypoxia and oxidative stress, activates neddylation in tumors, driving cancer progression.

Purpose of the Study:

  • To review the regulatory mechanisms and pathological features of neddylation in tumor evolution.
  • To explore the role of neddylation in therapeutic resistance.
  • To examine therapeutic strategies targeting NEDD8 modification for cancer treatment.

Main Methods:

  • Literature review of neddylation in cancer.
  • Analysis of regulatory mechanisms and pathological features.
  • Evaluation of therapeutic strategies targeting NEDD8.

Main Results:

  • Neddylation plays a critical role in sustaining tumorigenicity and cancer hallmarks.
  • Cellular stress triggers neddylation, promoting tumor initiation and progression.
  • Targeting neddylation presents novel therapeutic opportunities.

Conclusions:

  • Neddylation is a key player in tumor malignant evolution and therapeutic resistance.
  • Disrupting the neddylation cascade offers a promising approach for innovative cancer therapies.

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