Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1)

Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1) is a member of the RBR family of E3 ubiquitin ligases that mediates the transfer of ubiquitin and ubiquitin-like modifiers (e.g., ISG15) to diverse protein substrates through canonical (lysine) and non-canonical (serine) linkages. Activated by neddylated Cullin-RING ubiquitin ligase complexes, ARIH1 plays pivotal roles in regulating protein stability, cell signaling, and stress response pathways. It participates in DNA damage-induced translation arrest, antiviral immune signaling (especially via cGAS mono-ISGylation), mitophagy, and modulation of epithelial-mesenchymal transition and cancer stem cell properties, marking it as a relevant enzyme in cancer, immunity, and cell fate regulation. Frequent aliases include HHARI, ARI, ARI-1, and HARI. No drugs currently target ARIH1 directly, but its roles suggest therapeutic potential and biomarker utility in oncology, genotoxic stress, and antiviral therapies.

Other names

HHARIARIARI-1HARIMOP6UBCH7BPMonocyte protein 6Protein ariadne-1 homologUbcH7-binding proteinUbcM4-interacting proteinUbiquitin-conjugating enzyme E2-binding protein 1H7-AP2Ariadne, Drosophila, homolog ofAriadne homologHUSSY-27ARIH1

Potential future drugs might target ARIH1 by either inhibiting or enhancing its E3 ligase/ISGylase activities, thus modulating: Protein ubiquitination; ISGylation of antiviral proteins (e.g., cGAS); DNA damage response (protection against genotoxic stress); EMT and cancer stemness.