XAF1, also known as X-linked inhibitor of apoptosis (XIAP)-associated factor 1, belongs to the interferon (IFN)-induced gene family. It plays diverse roles in multiple biological processes. It is involved in apoptosis regulation, antiviral immunity, and is associated with various signaling pathways such as those related to AKT, type I interferon, and chromatin accessibility regulation [1-9]. Genetic models like knockout mouse models are valuable for studying its functions.

In XAF1-deficient mice, impaired induction of antiviral genes was observed, making them susceptible to RNA virus infections. This indicates XAF1's crucial role in promoting anti-RNA virus immune responses by regulating chromatin accessibility [1]. In colorectal cancer, XAF1 promotes metastasis via the VCP-RNF114-JUP axis [2]. Xaf1 knockout in mice leads to AKT activation in muscle and fat tissues, reducing body weight gain and insulin resistance, and accelerates spontaneous prostate tumorigenesis in mice with Pten heterozygous loss [3]. XAF1-knockout mice display resistance to viral infection, accompanied by increases in IFN-I production and IRF7 stability [4]. In osteoporosis and osteolysis mouse models, XAF1 knockout exacerbates bone loss due to increased osteoclast number and bone resorption [5].

In conclusion, XAF1 has essential functions in antiviral immunity, apoptosis regulation, and is involved in the pathogenesis of diseases such as cancer, diabetes, and bone-related disorders. Gene knockout mouse models have significantly contributed to understanding its role in these disease areas, providing insights into potential therapeutic targets.

References:

1. Kuang, Ming, Zhao, Yingchi, Yu, Haitao, Wang, Dandan, You, Fuping. 2023. XAF1 promotes anti-RNA virus immune responses by regulating chromatin accessibility. In Science advances, 9, eadg5211. doi:10.1126/sciadv.adg5211. https://pubmed.ncbi.nlm.nih.gov/37595039/

2. Xia, Ji, Ma, Ning, Shi, Qian, Long, Lingyun, Li, Jing-Jing. 2023. XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis. In The Journal of cell biology, 223, . doi:10.1083/jcb.202303015. https://pubmed.ncbi.nlm.nih.gov/38095639/

3. Chen, Min, Wang, Kangjunjie, Han, Ying, Qin, Jun, Gao, Daming. 2023. Identification of XAF1 as an endogenous AKT inhibitor. In Cell reports, 42, 112690. doi:10.1016/j.celrep.2023.112690. https://pubmed.ncbi.nlm.nih.gov/37384528/

4. Liu, Bao-Qin, Liu, Rong-Bei, Li, Wen-Ping, Jin, Jin, Li, Yi-Yuan. 2022. XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7. In EMBO reports, 24, e55387. doi:10.15252/embr.202255387. https://pubmed.ncbi.nlm.nih.gov/36394357/

5. Zhang, Mingchao, Huang, Yingkang, Bai, Jinyu, Ma, Feng, Zhou, Xiaozhong. 2024. XAF1 promotes osteoclast apoptosis by antagonizing the XIAP-caspase axis. In Journal of orthopaedic translation, 47, 15-28. doi:10.1016/j.jot.2024.05.001. https://pubmed.ncbi.nlm.nih.gov/38957269/