F-box only protein 6 (FBXO6)

F-box only protein 6 (FBXO6) is a member of the F-box protein family, distinguished by an approximately 40-amino-acid F-box motif. Within the cell, FBXO6 acts as a substrate recognition unit for the SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complex, targeting glycoproteins—including misfolded or unfolded proteins—and specific phosphorylated substrates for ubiquitination and subsequent proteasomal degradation. This protein is involved in protein quality control via the ER-associated degradation pathway, cell cycle regulation by degrading DNA damage checkpoint proteins such as CHEK1, and is implicated in mitotic control via interactions with spindle checkpoint proteins Mad2 and BubR1. FBXO6 has a notable role in ovarian cancer, where its overexpression correlates with poor prognosis, and its activity is linked to modulation of tumor suppressors such as RNASET2. The protein is widely expressed across tissues, and while drug discovery efforts are ongoing, no clinical drugs directly target FBXO6 to date. Dysfunction in FBXO6 is associated with cancer and glycosylation disorders, reflecting its critical regulatory functions in cell cycle progression and protein homeostasis.

Other names

F-box only protein 6FBXO6FBG2FBS2FBX6Fbx6bF-box/G-domain protein 2F-box protein FBG2F-box protein Fbx6F-box protein that recognizes sugar chains 2

Inhibition: Would block ubiquitination of glycoprotein substrates or downstream tumor suppressors (e.g., RNASET2, CHEK1), potentially reactivating their tumor-suppressive functions. Activation: Would enhance degradation of misfolded glycoproteins or checkpoint proteins, possibly used to clear toxic protein aggregates or regulate cell cycle checkpoints.