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...

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Published in:Trends in biochemical sciences (Amsterdam. Regular ed.) 2014-06, Vol.39 (6), p.260-267
Main Authors: Silva, Jerson L., Gallo, Claudia V. De Moura, Costa, Danielly C.F., Rangel, Luciana P.
Format: Article
Language:English
Subjects:
amyloid
Amyloid - chemistry
Animals
cancer
Humans
Mutant Proteins - metabolism
Mutation - genetics
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - therapy
p53
prion
prion-like proteins
Prions - chemistry
Prions - metabolism
protein aggregation
Protein Multimerization
Tumor Suppressor Protein p53 - chemistry
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary:•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.
ISSN:0968-0004
1362-4326
DOI:10.1016/j.tibs.2014.04.001