Physiological functions of FBW7 in cancer and metabolism

FBW7 is one of the most well characterized F-box proteins that serve as substrate recognition subunits of SCF (Skp1-Cullin 1-F-box proteins) E3 ubiquitin ligase complexes. SCFFBW7 plays key roles in regulating cell cycle progression, differentiation, and stem cell maintenance largely through targeting a broad range of oncogenic substrates for proteasome-dependent degradation. The identification of an increasing number of FBW7 substrates for ubiquitination, and intensive in vitro and in vivo studies have revealed a network of signaling components controlled by FBW7 that contributes to metabolic regulation as well as its tumor suppressor role. Here we mainly focus on recent findings that highlight a critical role for FBW7 in cancer and metabolism. •Physiological role of FBW7 in cellular maintenance through regulating differentiation, stemness, and metabolism.•Targeting aberrant FBW7 signaling is a promising anti-cancer therapeutic strategy•FBW7 is involved in the regulation of circadian rhythm associated with hepatic metabolism and energy homeostasis.