<b>Conclusions:</b> This survey of p53-targeting ubiquitin ligases provides a roadmap for potential therapeutic strategies working by promoting the destruction of the mutant protein or reactivating its normal function in <i>TP53</i>-mutated colorectal cancers and promoting p53 function by preventing degradation in <i>TP53</i> wild-type cancers. The gene discussed is TP53; the disease is cancer.