Although this may be in part due to E1A-induced p14ARF, which inhibits the E3 ligase activity of MDM2 [47], this is also reminiscent of the tumor specific escape of mutant p53 from Mdm2 degradation in mice harboring germ line p53 mutations, an observation that suggests the existence of additional mechanisms for modulating the p53-MDM2 loop during tumorigenesis [29,30]. This evidence concerns the gene DHTKD1 and neoplasm.