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TP53: an oncogene in disguise.

T Soussi1, K G Wiman2

  • 11] Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska (CCK) R8:04, Stockholm SE-171 76, Sweden [2] Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France [3] INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France [4] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Cell Death and Differentiation
|May 30, 2015
PubMed
Summary

The tumor protein p53 (TP53) gene, traditionally viewed as a tumor suppressor, exhibits significant oncogenic properties. Many TP53 mutants function as oncoproteins, highlighting its atypical role in cancer development and as a therapeutic target.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The tumor protein p53 (TP53) is conventionally classified as a tumor suppressor gene.
  • Emerging evidence indicates that numerous p53 mutants possess oncogenic functions.

Purpose of the Study:

  • To challenge the traditional view of TP53 as solely a tumor suppressor.
  • To emphasize the oncogenic properties of TP53 mutants and their therapeutic potential.

Main Methods:

  • Review of TP53 mutation signatures in human cancers.
  • Analysis of gain-of-function (GOF) activities of p53 mutants.
  • Examination of phenotypes in mouse models of TP53 mutations.

Main Results:

  • TP53 mutations are frequent in human cancers, with hotspot mutants acting as common oncoproteins.
  • p53 mutants display diverse oncogenic properties and lead to heterogeneous phenotypes.
  • Muller's mutation classification aids in assessing TP53's atypical cancer gene behavior.

Conclusions:

  • TP53 is an atypical cancer gene with significant oncogenic functions beyond tumor suppression.
  • Understanding the oncogenic roles of TP53 mutants is crucial for developing targeted cancer therapies.