Prion-like aggregation of mutant p53 in cancer.

Trends Biochem Sci

Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia (INCT) de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Published: June 2014

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.

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Source
http://dx.doi.org/10.1016/j.tibs.2014.04.001DOI Listing

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