MDM2 and cancer: This unexpectedly low rate may be influenced by Thai genetic predispositions to cancer. Mdm2 is the major negative regulator of p53, the key tumor suppressor involved in the tumorigenesis of the majority of human cancers. Mdm2 is proposed to regulate p53 at the posttranslational level by enhancing p53 degradation through E3 ligase activity [29–31].