F-box protein 3 (FBXO3)

F-box protein 3 (FBXO3) is an E3 ubiquitin ligase enzyme, belonging to the F-box protein family and a substrate recognition subunit of the SCF ubiquitin-protein ligase complex. It mediates ubiquitination and degradation of specific proteins such as FBXL2, HIPK2, and potentially EP300, thus regulating inflammation, immune responses, cell cycle, DNA damage response, apoptosis, and cancer progression. FBXO3 interacts with viral and cellular proteins and is implicated in the regulation of antiviral immunity and host defense. Its overexpression is associated with several cancers, autoimmune diseases, and neuropathic conditions. Structurally, FBXO3 contains an F-box domain and an ApaG domain. The latter is involved in substrate recognition for ubiquitination, and may represent a potential drug discovery target for modulating inflammation and malignancies[1][2][3][4]. FBXO3 is considered a therapeutic target due to its central roles in inflammation, oncogenesis, immune regulation, and its specific involvement in diseases such as cancer and rheumatoid arthritis[1][4]. There are currently few known direct drugs besides HDAC inhibitors like belinostat that modulate FBXO3, but research is ongoing for targeting its activity in various conditions.

Other names

F-box only protein 3FBX3F-box protein FBX3FBXO3FBA

Drugs may act via modulation of FBXO3 transcription, stabilization, or E3 ligase activity (e.g., Belinostat increases FBXO3 expression, promoting apoptosis and reducing drug resistance)