NEDD8 and lung cancer: To further determine whether FBXW2 is a substrate of SCF E3, we treated lung cancer A549 cells with MLN4924, a small molecule inhibitor of NEDD8-activating enzyme, which inactivates SCF E3 by inhibiting cullin-1 neddylation51, and found MLN4924 causes a dose-dependent accumulation of FBXW2 (Supplementary Fig. 1b).