Here, we identified and characterized DEPTOR as a novel, direct downstream target of the tumor suppressor, p53, based on the following lines of evidence: (1) the protein and mRNA levels of DEPTOR were positively correlated with p53 activity in both cultured cancer cells and mouse tissues; (2) a typical p53 consensus binding site (–196 ~–169, C-DEPTOR) was identified in the DEPTOR promoter; and (3) p53 bound to C-DEPTOR and activated DEPTOR transcription, as determined by dual-luciferase reporter and ChIP assays. The gene discussed is TP53; the disease is cancer.