Mutant p53 gain-of-function in cancer

Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a001107. doi: 10.1101/cshperspect.a001107.


In its wild-type form, p53 is a major tumor suppressor whose function is critical for protection against cancer. Many human tumors carry missense mutations in the TP53 gene, encoding p53. Typically, the affected tumor cells accumulate excessive amounts of the mutant p53 protein. Various lines of evidence indicate that, in addition to abrogating the tumor suppressor functions of wild-type p53, the common types of cancer-associated p53 mutations also endow the mutant protein with new activities that can contribute actively to various stages of tumor progression and to increased resistance to anticancer treatments. Collectively, these activities are referred to as mutant p53 gain-of-function. This article addresses the biological manifestations of mutant p53 gain-of-function, the underlying molecular mechanisms, and their possible clinical implications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Animals
  • Apoptosis*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic*
  • Genes, p53*
  • Humans
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neoplasm Metastasis
  • Neoplasms / genetics*
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics*


  • TP53 protein, human
  • Tumor Suppressor Protein p53