First, an enhanced potency of MDM4-S to inhibit wt p53 activity (Rallapalli et al., 2003) was claimed to be a significant cancer risk (Rallapalli et al., 1999), which accounted for its high levels in numerous cancers (Bartel et al., 2005; Lenos et al., 2012; Liu et al., 2012). Here, TP53 is linked to cancer.