Prion-like aggregation of mutant p53 in cancer.
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.
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. Electronic address: jerson@bioqmed.ufrj.br.
Jerson L
JL
Silva
Instituto Nacional de Ciência e Tecnologia (INCT) de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; Departamento de Genética, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Claudia V
CV
De Moura Gallo
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.
Danielly C F
DC
Costa
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.
Luciana P
LP
Rangel
D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D000682:Amyloid; D050505:Mutant Proteins; D011328:Prions; D016159:Tumor Suppressor Protein p53
amyloid; cancer; p53; prion; prion-like proteins; protein aggregation