Although we showed CUL7FBXW11 is the E3 ligase of TET2 in NSCLC, other potential E3 ligase or substrate receptor of TET2 may exist in other cell types, such as immune cells.34,38 In our results, MLN4924 partially but not completely rescued the TET2 level caused by MEK1 knockout in NSCLC cells (Supplementary Fig. 5f), indicating other potential non-cullin-based E3 ligase of TET2 may also involve in this resistant mechanism, which warrants future study. The gene discussed is CACUL1; the disease is non-small cell lung carcinoma.