RNF123, a RING finger protein, functions as an E3 ubiquitin ligase and is involved in multiple biological processes. It plays roles in innate immune response regulation, cell cycle control, and glycolysis, among others. It is associated with pathways such as Toll-like receptor 3 (TLR3)-and interferon (IFN) regulatory factor 7 (IRF7)-mediated type I IFN production, and its dysregulation is linked to diseases like laminopathies, breast cancer, and glioblastoma [1,3,4]. Genetic models, especially gene knockout models, are valuable for studying its functions in vivo.

In a rodent malaria model, RNF123-deficient mice showed significantly lower levels of parasitemia and mortality after infection with Plasmodium yoelii 17XL, indicating that erythrocytic RNF123 is involved in susceptibility to rodent malaria infection [2]. In breast cancer, overexpression of RNF123 decreased cell viability, colony-forming ability, and glycolytic activity, and induced ubiquitination of PFKP, suggesting its role as a tumor suppressor [3].

In summary, RNF123 is a multifunctional E3 ubiquitin ligase with essential roles in immune response, cell growth, and disease-related processes. Gene knockout mouse models have been crucial in uncovering its functions in malaria susceptibility and breast cancer, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Huang, Shanzhi, Cui, Min, Huang, Juan, Jing, Bo, Jia, Renyong. 2023. RNF123 Mediates Ubiquitination and Degradation of SOCS1 To Regulate Type I Interferon Production during Duck Tembusu Virus Infection. In Journal of virology, 97, e0009523. doi:10.1128/jvi.00095-23. https://pubmed.ncbi.nlm.nih.gov/37014223/

2. Miyasaka, Yuki, Niwa, Shota, Masuya, Tomomi, Horio, Fumihiko, Ohno, Tamio. 2022. E3 ubiquitin ligase RNF123-deficient mice exhibit reduced parasitemia and mortality in rodent malaria (Plasmodium yoelii 17XL) infection. In Parasitology international, 88, 102542. doi:10.1016/j.parint.2022.102542. https://pubmed.ncbi.nlm.nih.gov/35063657/

3. Chen, Xiaoqing, Su, Weijie, Chen, Jiewen, Ouyang, Peng, Gong, Jin. 2024. RNF123 inhibits cell viability, cell cycle and colony formation of breast cancer by inhibiting glycolysis via ubiquitination of PFKP. In Naunyn-Schmiedeberg's archives of pharmacology, , . doi:10.1007/s00210-024-03723-2. https://pubmed.ncbi.nlm.nih.gov/39725718/

4. Khanna, Richa, Krishnamoorthy, Vidhya, Parnaik, Veena K. 2018. E3 ubiquitin ligase RNF123 targets lamin B1 and lamin-binding proteins. In The FEBS journal, 285, 2243-2262. doi:10.1111/febs.14477. https://pubmed.ncbi.nlm.nih.gov/29676528/