Fbxo44, an F-box protein, is involved in multiple biological functions. It functions as an E3 ubiquitin ligase, playing a role in protein degradation processes, which are crucial for maintaining normal cellular function. It is associated with pathways such as the ubiquitin-proteasome system, and is important in various biological contexts, including cancer and other diseases [3,5,6]. Genetic models, like gene knockout models, can be valuable for studying its functions in vivo.

In cancer cells, FBXO44 promotes DNA replication-coupled repetitive element (RE) silencing. Inhibition of FBXO44 or its co-factor SUV39H1 reactivates REs, leading to DNA replication stress, activation of antiviral pathways and interferon signaling, decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response. FBXO44 expression inversely correlates with replication stress, antiviral pathways, IFN signaling, and cytotoxic T cell infiltration in human cancers. FBXO44 was also found to promote tumor progression and metastasis in adenocarcinoma of the esophagogastric junction [1,2]. Additionally, FBXO44-mediated degradation of proteins like RGS2, PXR, and BRCA1 has been reported. Inhibiting the RGS2-FBXO44 interaction could be a therapeutic approach for diseases associated with RGS2 dysregulation [3,4,5,6].

In conclusion, Fbxo44 is essential in regulating protein levels through ubiquitination-mediated degradation and in controlling RE transcription in cancer cells. The study of Fbxo44 using gene knockout or other genetic models has contributed to understanding its role in cancer development, progression, and potential immunotherapy responses. Additionally, its involvement in diseases related to protein dysregulation, such as those associated with RGS2, highlights its significance in multiple disease areas.