Moreover, we showed that RBPJ/DAPK3 axis regulated the activity of UBE3A, and RBPJ inhibitors enhanced the antitumor effect of CDK4/6 inhibitors by regulating the DAPK3/UBE3A axis in RCC, which provides a clue for targeted therapy of RCC. The gene discussed is RBPJ; the disease is renal cell carcinoma.