Prominent exceptions are ligases frequently mutated in cancer such as MDM2, FBXW7, VHL, KEAP1 and BRCA1, as well as E3 ligases found in genome-wide association studies and phenotypic screens (for instance Parkin, ITCH) as well as serendipitous discoveries such as CRBN as a target of thalidomide [13]. This evidence concerns the gene MDM2 and cancer.