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<p>Melanoma is an aggressive type of cancer that is prone to developing resistance to targeted therapies and immunotherapies, so it is necessary to seek novel therapeutic opportunities. RING finger E3 ubiquitin ligases (RNFs) play a crucial role in the ubiquitin–proteasome system and are important in regulating the development of melanoma by orchestrating various pathways. In this review, we analyze the structural and functional characteristics of the RNF subfamily to clarify their mechanisms of action in melanoma and to compare the functional differences among various RNFs. Additionally, we systematically evaluate potential therapeutic strategies targeting RNFs, including small-molecule drugs, proteolysis-targeting chimeras (PROTACs), and molecular glues, and further propose new directions for drug design by using computer-aided technology. Furthermore, this review suggests that RNF-targeted therapy should be combined with existing therapies, providing a novel approach for the precise treatment of melanoma, and is significant for clinical application and drug development.</p>

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RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Ji-fang Zhang,
  • Long-tian Li,
  • Yue-ying Yang,
  • Shi-chen Zhang,
  • Chao Gao,
  • Xu Zhu,
  • He Xin,
  • Xin-yang Li

摘要

Melanoma is an aggressive type of cancer that is prone to developing resistance to targeted therapies and immunotherapies, so it is necessary to seek novel therapeutic opportunities. RING finger E3 ubiquitin ligases (RNFs) play a crucial role in the ubiquitin–proteasome system and are important in regulating the development of melanoma by orchestrating various pathways. In this review, we analyze the structural and functional characteristics of the RNF subfamily to clarify their mechanisms of action in melanoma and to compare the functional differences among various RNFs. Additionally, we systematically evaluate potential therapeutic strategies targeting RNFs, including small-molecule drugs, proteolysis-targeting chimeras (PROTACs), and molecular glues, and further propose new directions for drug design by using computer-aided technology. Furthermore, this review suggests that RNF-targeted therapy should be combined with existing therapies, providing a novel approach for the precise treatment of melanoma, and is significant for clinical application and drug development.