Molecular Cancer (Jul 2024)

Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches

  • Fangfang Liu,
  • Jingyu Chen,
  • Kai Li,
  • Haochen Li,
  • Yiyi Zhu,
  • Yubo Zhai,
  • Bingbing Lu,
  • Yanle Fan,
  • Ziyue Liu,
  • Xiaojie Chen,
  • Xuechao Jia,
  • Zigang Dong,
  • Kangdong Liu

DOI
https://doi.org/10.1186/s12943-024-02046-3
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 50

Abstract

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Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin–proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.

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