TSC1 and nonpapillary renal cell carcinoma: Given that CDK4/6 inhibitors regulate the stability of TSC1 (Fig. 1) and that CDK4-mediated phosphorylation of RNF26 promotes RNF26 binding with TSC1 in ccRCC cells (Fig. 2), we showed that knockdown of RNF26 diminished the TSC1 protein level change induced by overexpression/knockdown of CDK4 or treatment with CDK4/6 inhibitors in 786-O and A498 cells (Fig. 6m, Supplementary Fig. 3a, b).