TP53: an oncogene in disguise

The standard classification used to define the various cancer genes confines tumor protein p53 (TP53) to the role of a tumor suppressor gene. However, it is now an indisputable fact that many p53 mutants act as oncogenic proteins. This statement is based on multiple arguments including the mutation...

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Bibliographic Details
Published in:Cell death and differentiation 2015-08, Vol.22 (8), p.1239-1249
Main Authors: Soussi, T, Wiman, K G
Format: Article
Language:English
Subjects:
631/67/581
Animals
Apoptosis
Aza Compounds - metabolism
Biochemistry
Biomarkers
Biomedical and Life Sciences
Bridged Bicyclo Compounds, Heterocyclic - metabolism
Cancer
Cell Biology
Cell Cycle Analysis
Cell death
Cell growth
Chromosomes
Classification
Genes
Genomes
Genotype & phenotype
Humans
Kinases
Life Sciences
Maleimides - metabolism
Medicin och hälsovetenskap
Mutation
Mutation - genetics
Oncology
Phenotype
Polypeptides
Proteins
Review
Sarcoma
Stem Cells
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumors
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Summary:The standard classification used to define the various cancer genes confines tumor protein p53 (TP53) to the role of a tumor suppressor gene. However, it is now an indisputable fact that many p53 mutants act as oncogenic proteins. This statement is based on multiple arguments including the mutation signature of the TP53 gene in human cancer, the various gains-of-function (GOFs) of the different p53 mutants and the heterogeneous phenotypes developed by knock-in mouse strains modeling several human TP53 mutations. In this review, we will shatter the classical and traditional image of tumor protein p53 (TP53) as a tumor suppressor gene by emphasizing its multiple oncogenic properties that make it a potential therapeutic target that should not be underestimated. Analysis of the data generated by the various cancer genome projects highlights the high frequency of TP53 mutations and reveals that several p53 hotspot mutants are the most common oncoprotein variants expressed in several types of tumors. The use of Muller’s classical definition of mutations based on quantitative and qualitative consequences on the protein product, such as ‘amorph’, ‘hypomorph’, ‘hypermorph’ ‘neomorph’ or ‘antimorph’, allows a more meaningful assessment of the consequences of cancer gene modifications, their potential clinical significance, and clearly demonstrates that the TP53 gene is an atypical cancer gene.
ISSN:1350-9047
1476-5403
1476-5403
DOI:10.1038/cdd.2015.53