PI3K-dependent phosphorylation of Fbw7 modulates substrate degradation and activity

► Human Fbw7alpha is phosphorylated at Ser227 in a PI3K-dependent manner. ► Subcellular localization and known interactions of Fbw7 are not affected. ► Ser227 phosphorylation stabilizes Fbw7 and enhances substrate degradation. ► Ser227 phosphorylation regulates Fbw7 to fine-tune substrate levels and activity.