The enigma of the RING-UIM E3 ligases: its transformative impact on cancer research

RING-UIM E3 ligases, a subfamily within the RING-type E3 ligases, comprise four members: RNF114, RNF125, RNF138, and RNF166. These ligases are crucial in various biological processes, including immunity, inflammation, epigenetics, and homologous recombination. Extensive research has demonstrated that RING-UIM E3 ligases fulfill specific biological roles in carcinogenesis by ubiquitinating critical oncogenes and tumor suppressors, thereby modulating various signaling pathways, differing their functions across distinct cancer contexts. This review comprehensively examines the multifaceted roles of RING-UIM E3 ligases in human cancers, elucidates the molecular mechanisms underpinning their actions and regulatory effects on cancer cells, and explores their potential clinical applications.