Probable E3 ubiquitin-protein ligase Deltex-2 (DTX2)

Probable E3 ubiquitin-protein ligase Deltex-2 (DTX2) is a member of the human Deltex family, functioning as a RING-type E3 ubiquitin ligase—the enzyme catalyzing the final step of the ubiquitination cascade, transferring ubiquitin from an E2 enzyme to substrate proteins[1][4][5]. DTX2 contains tandem WWE domains that recognize poly-ADP-ribosylated (PARylated) substrates; its C-terminal DTC domain binds ADP-ribose and recruits proteins for ubiquitination, especially those involved in the DNA damage response (DDR)[5]. DTX2 is rapidly mobilized to DNA double-strand breaks in a poly ADP-ribosylation-dependent manner and regulates the balance between homologous recombination and nonhomologous end joining: its depletion impairs HR repair (including BRCA1 foci formation) and increases NHEJ, affecting repair pathway choice and genomic stability in cancer cells[2]. DTX2 is implicated in signal transduction, protein turnover, cell growth, differentiation, apoptosis, and the development of various tumors[1][4]. Drugs such as PARP inhibitors hinder DTX2 recruitment to DNA damage sites by blocking substrate PARylation[5]. DTX2 is under investigation as a modulator of genomic stability and a potential therapeutic target in oncology, especially for interventions targeting DNA repair mechanisms or PARP activity[2][5].

Other names

Probable E3 ubiquitin-protein ligase DTX2KIAA1528RNF58Deltex2hDTX2Protein deltex-2RING finger protein 58RING-type E3 ubiquitin transferase DTX2Deltex homolog 2zinc ion binding protein

Drugs inhibiting PARP1/PARP2 indirectly affect DTX2 function by modulating PARylation of its substrates, preventing DTX2 recruitment to DNA damage sites and ubiquitination of PARylated proteins.