Arih1-KO Mouse

Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) is an E3 ubiquitin ligase. It plays crucial roles in multiple biological processes by regulating protein ubiquitination and degradation, which are involved in immune responses, cell-cycle regulation, and cancer-related pathways [1-3, 5, 9]. It is associated with pathways like the STING pathway, antiviral immunity, and anti-tumor immunity [1,3,4]. Genetic models, such as KO or CKO mouse models, can be valuable in studying its functions in vivo.

In cancer research, cisplatin-induced upregulation of ARIH1 in tumors enhances the anti-tumor effect of PD-L1 blockade. ARIH1 overexpression promotes cytotoxic T-cell infiltration and inhibits tumor growth. It mediates ubiquitination and degradation of DNA-PKcs to trigger the STING pathway activation, and this can be blocked by certain cGAS mutants [1]. ARIH1 also targets PD-L1 for proteasomal degradation, and its overexpression suppresses tumor growth and promotes cytotoxic T-cell activation in wild-type mice [2]. In antiviral immunity, knockdown or knockout of ARIH1 in mice significantly inhibits herpes simplex virus 1 (HSV-1)-or cytoplasmic DNA-induced expression of type I interferons (IFNs) and proinflammatory cytokines. Tamoxifen-treated ER-Cre;Arih1fl/fl mice and Lyz2-Cre; Arih1fl/fl mice are hypersensitive to HSV-1 infection [3]. In influenza A virus infection, ARIH1 enhances IFN-β and downstream gene expression by affecting the degradation of RIG-I through the SQSTM1/p62 signaling pathway [4].

In conclusion, ARIH1 is an important E3 ubiquitin ligase that is involved in anti-tumor and antiviral immunity. The use of KO/CKO mouse models has revealed its role in these processes, providing insights into the mechanisms of cancer and viral infections. These findings suggest that modulating ARIH1 could be a potential strategy for cancer immunotherapy and treating viral infections [1-3, 5].