F-box and leucine-rich repeat protein 8 (FBXL8)

F-box and leucine-rich repeat protein 8 (FBXL8) is a member of the F-box protein family, defined by the F-box motif and leucine-rich repeats. As part of the SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complex, FBXL8 serves as a substrate recognition component, targeting specific proteins for ubiquitin-mediated degradation in a phosphorylation-dependent manner. FBXL8 controls cell cycle progression, particularly through degradation of phosphorylated cyclin D3, thus influencing cell proliferation and tumorigenesis. In cancer, FBXL8 functions as a tumor suppressor in some contexts (e.g., lymphoma), but its overexpression promotes progression and poor prognosis in breast cancer, potentially through turnover of tumor suppressor proteins (e.g., CCND2, IRF5) and modulation of DNA repair and immune signaling pathways. FBXL8’s molecular interactions and substrate specificity are defined by its highly ordered leucine-rich repeat domain. No clinically approved drugs, known selective inhibitors, or safety data exist for FBXL8-targeted therapeutics at this time.

Other names

F-box/LRR-repeat protein 8FBXL8FBL8F-box protein FBL8F-box and leucine-rich repeat protein 8

Drugs or interventions targeting FBXL8 would be expected to: Modulate protein ubiquitination/degradation, particularly of cell cycle proteins like cyclin D3, CCND2 (cyclin D2), IRF5; Alter cell cycle progression by affecting substrate degradation (inhibition or enhancement).