Prion-like aggregation of mutant p53 in cancer

• Prion-like aggregation of mutant p53 offers a novel mechanism of cancer pathogenesis.
• The dominant-negative effects of p53 mutants are related to prion-like behavior.
• Prion-like aggregation of p53 mutants explains their gain-of-function effects.
• Prion-like aggregation of p53 mutants is a potential new therapeutic target.

p53 is a master regulatory protein that participates in cellular processes such as apoptosis, DNA repair, and cell cycle control. p53 functions as a homotetrameric tumor suppressor, and is lost in more than 50% of human cancers. Recent studies have suggested that the formation of mutant p53 aggregates is associated with loss-of-function (LoF), dominant-negative (DN), and gain-of-function (GoF) effects. We propose that these phenomena can be explained by a prion-like behavior of mutant p53. We discuss the shared properties of cancer and neurodegenerative diseases and how the prion-like properties of p53 aggregates offer potential targets for drug development.