Several ITCH-related HECT family members (e.g., Smurf1, Smurf2, WWP1 Nedd4) and their protein substrates (e.g., Notch1, SMAD2, PTEN, p53) are involved in tumorigenesis (13) and may serve as promising targets for cancer therapies. The gene discussed is NEDD4; the disease is cancer.