RB1 and melanoma: Nutlin-3 downregulation of RB was also observed in melanoma cell lines, and E2F1 levels dictate nutlin-3 sensitivity: sensitive melanoma cells accumulated MDM2, inducing p21 and lowering E2F1 levels, whereas resistant cells accumulated MDM2 but maintained E2F1 and showed less potent upregulation of p21 [112].