Denticleless E3 ubiquitin protein ligase adapter (DTL)

Denticleless E3 ubiquitin protein ligase adapter (DTL) is a substrate-specific adapter protein within the CRL4(DDB1) E3 ubiquitin ligase complex, acting as a key regulator in cell cycle progression, DNA damage response, and genomic stability. DTL mediates the ubiquitin-dependent degradation of critical cell cycle regulators such as CDT1, p21, SET8, and others, primarily by interacting with proliferating cell nuclear antigen (PCNA), thus preventing DNA over-replication and ensuring proper checkpoint control. DTL is frequently overexpressed in multiple cancers, and its deregulated activity drives cell proliferation, migration, invasion, and is associated with poor prognosis and chemoresistance. As a potential therapeutic target and biomarker, DTL's inhibition suppresses tumor cell proliferation independent of TP53 status and its overexpression correlates with aggressive disease features.

Other names

Denticleless protein homologCDT2CDW1DCAF2L2DTLRAMPDDB1- and CUL4-associated factor 2Retinoic acid-regulated nuclear matrix-associated proteinlethal(2) denticleless protein homolog

Drugs targeting DTL would likely function by inhibiting its role in the CRL4(CDT2) ubiquitin ligase complex, affecting cell cycle progression, and disrupting protein degradation pathways important for cancer cell survival.