We have identified a number of ubiquitin and ubiquitin-like ligases that are amplified in TCGA datasets and show evidence of cancer driver activity, including MDM2, DCUN1D1 and PIAS3. Of these genes, the best characterized is MDM2, a E3 ubiquitin ligase that mediates p53 polyubiquitylation and degradation, allowing for silencing of p53 in p53-wild type cancer cells [45]. This evidence concerns the gene PIAS3 and cancer.