DTX3 (deltex E3 ubiquitin ligase 3) is a RING domain-containing E3 ubiquitin ligase that primarily functions as a tumor suppressor through regulation of multiple signaling pathways 1. The protein's primary mechanism involves ubiquitination and degradation of key oncogenic targets, particularly components of the Notch signaling pathway. DTX3 directly binds to the Notch intracellular domain (NICD) via its C-terminal RING finger domain, promoting NICD ubiquitination and proteasomal degradation 2. This leads to suppression of Notch signaling and inhibition of tumor cell proliferation, migration, and invasion 32. Additionally, DTX3 regulates cell cycle progression by modulating E2F1 transcriptional activity and its downstream targets CDC2 and Cyclin D3 4. Notably, DTX3 exhibits unique enzymatic properties among DELTEX family members, including the ability to ubiquitinate nucleic acids directly and ADP-ribosylated DNA/RNA substrates 56. Clinically, DTX3 expression is consistently downregulated in multiple cancer types including esophageal, bladder, colorectal, and breast cancers, with low expression correlating with poor prognosis 3247. This positions DTX3 as both a potential prognostic biomarker and therapeutic target for cancer treatment.