MDM2 and cancer: While mutations of p53 are observed in more than half of human tumors [83], dysregulation of the ARF tumor-suppressor protein (p14ARF in humans and p19ARF in mouse), which increases and activates wild-type p53 by sequestering Mdm2 in the nucleolus [84] or by directly inhibiting the enzymatic activity of Mdm2 [85, 86], is a common characteristic in cancer as well.