DTX3L E3 ligase: Molecular functions, regulatory mechanisms, and potential as a novel cancer biomarker and therapeutic target.

The ubiquitin-proteasome pathway is a critical regulatory system in eukaryotic cells, which mediates dynamic and reversible protein modifications through the E1-E2-E3 ubiquitination cascade. E3 ubiquitin ligases, which catalyze substrate-specific ubiquitination for proteasomal degradation, play essential roles in maintaining cellular homeostasis. The deltex E3 ubiquitin ligase 3 L (DTX3L) modulates a variety of biological processes, such as proliferation, cell cycle, migration, invasion and apoptosis. Emerging evidence implicates DTX3L dysregulation in the pathogenesis of multiple malignancies, including cervical cancer, melanoma, prostate cancer, triple-negative breast cancer, glioma and pancreatic cancer. This review synthesizes current knowledge on DTX3L's molecular mechanisms across tumor types, highlighting its role in modulating the stability of oncogenic and tumor-suppressive substrates. As DTX3L emerges as a promising oncology therapeutic target, its molecular functions and regulatory mechanisms offers novel opportunities for rational antitumor drug design. However, the clinical translatability of DTX3L-targeted strategies requires further validation. In conclusion, DTX3L has the potential to serve as a novel cancer biomarker and therapeutic target.