We thus set out in this study to identify and characterize distinct regulatory motifs that can give rise to variable signaling outputs of p53 pathway in a broad cellular context, using three anticancer chemotherapeutics that activate p53 via distinct mechanisms, including Etoposide (DNA damage inducer), Nutlin-3a (Mdm2 inhibitor), and 5-fluorouracil (nucleolar stress inducer), and five human cancer cell lines. This evidence concerns the gene TP53 and cancer.