We then used MLN4924, a small molecule inhibitor of NAE (NEDD8-Activating Enzyme), which indirectly inhibits the entire CRL E3 ligases by blocking cullin neddylation24, and found a dose-dependent accumulation of β-TrCP1 in all three lung cancer cell lines tested (Figs 2F and S2B,C), further supporting the notion that β-TrCP1 is a novel substrate of CRLs. This evidence concerns the gene BTRC and lung cancer.