p53, A Victim of the Prion Fashion

SIMPLE SUMMARY: The tumor suppressor gene TP53 is found mutated in around half of human cancers. The accumulation of the mutant p53 protein in the form of aggregates in cancer cells have led to the emergence of the “prion p53” hypothesis which states that mutant p53 is able to drive the wild-type form of the protein into an alternate conformation, thereby contributing to tumor progression. This report challenges the “prion p53” hypothesis by reviewing evidence of p53 behavior in light of our current knowledge regarding amyloid proteins, prionoids and prions. ABSTRACT: Identified in the late 1970s as an oncogene, a driving force leading to tumor development, p53 turned out to be a key tumor suppressor gene. Now p53 is considered a master gene regulating the transcription of over 3000 target genes and controlling a remarkable number of cellular functions. The elevated prevalence of p53 mutations in human cancers has led to a recurring questioning about the roles of mutant p53 proteins and their functional consequences. Both mutants and isoforms of p53 have been attributed dominant-negative and gain of function properties among which is the ability to form amyloid aggregates and behave in a prion-like manner. This report challenges the ongoing “prion p53” hypothesis by reviewing evidence of p53 behavior in light of our current knowledge regarding amyloid proteins, prionoids and prions.