F-box and WD repeat-containing protein 4 (FBXW4)

F-box and WD repeat-containing protein 4 (FBXW4) is a substrate-recognition subunit of the SCF (SKP1–Cullin–F-box) E3 ubiquitin ligase complex that mediates the ubiquitination and targeted degradation of regulatory proteins[1][2][5][7]. FBXW4 is essential for proper limb development, as mutations in the gene cause split hand/foot malformation (SHFM3) in humans and analogous limb defects in mice[1][5][7]. In cancer biology, especially acute myeloid leukemia (AML), high FBXW4 expression has been associated with older age, more adverse clinical risk profiles, and poor overall survival outcomes, indicating it may serve as a prognostic biomarker and a potential therapeutic target[2][3]. While no specific drugs against FBXW4 are approved, its role in the ubiquitin ligase system aligns it pharmacologically with targets susceptible to proteasome or cullin-ligase inhibitors[2][3]. The multifaceted functions of FBXW4 thus include both developmental and oncogenic contexts, mediated by its control of proteostasis and intersection with key cellular regulatory pathways.

Other names

DactylinSHFM3FBW4FBWD4SHSF3F-box and WD repeat domain containing 4F-box and WD-40 domain protein 4

Inhibition of SCF E3 ubiquitin ligase activity (for indirect approaches like Pevonedistat, not FBXW4-specific)