E3 ligases that have been shown to function as tumor suppressors in HCC include the mouse double minute 2 (MDM2) and BRCA1, which target p53 for ubiquitination and degradation135; Smad ubiquitinization regulatory factor-2 (Smurf-2), which targets Smad proteins and the TGFβ receptor complex for degradation136; and the FRA6E fragile site protein Parkin, which targets cyclin E and P38137. Here, TP53 is linked to hepatocellular carcinoma.