Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) belongs to the RBR class of E3 ubiquitin ligases. It has diverse functions, being involved in multiple biological processes and signaling pathways. ARIH1 plays a significant role in immune-related processes, antiviral immunity, and is associated with cancer-related pathways, which are crucial for understanding disease mechanisms. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions in vivo [3,4].

In immune-related studies, ARIH1 knockout or knockdown in mice has shown its importance in antiviral immunity. For example, deletion of ARIH1 in myeloid cells alleviates autoimmune phenotypes and rescues autoimmune lethality caused by TREX1 deficiency, indicating its role in innate autoimmune responses [3].

In the context of cancer, overexpression of ARIH1 promotes cytotoxic T-cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. It mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, and its loss is related to immune checkpoint blockade (ICB) resistance in tumors [1]. Additionally, ARIH1 is identified as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation, highlighting its role in anti-tumor immunity [2]. In breast cancer, ARIH1 silencing leads to increased hnRNP-E1 protein stability, delayed EMT induction, reduced invasion, and attenuated cancer cell stemness in vitro and tumor formation in vivo, suggesting its role in cancer progression [5].

In conclusion, ARIH1 is a key E3 ubiquitin ligase involved in antiviral and autoimmune responses, as well as in cancer-related processes. Studies using KO/CKO mouse models have revealed its role in specific disease conditions, such as autoimmune diseases and cancer, providing insights into potential therapeutic strategies targeting ARIH1-related pathways.