When mutant p53 plays hide and seek: a new challenge for diagnosis and therapy?

Trends Mol Med. 2009 Jan;15(1):1-4. doi: 10.1016/j.molmed.2008.11.002. Epub 2008 Dec 25.


p53 missense mutations observed in human cancers are often associated with an increased level of p53 protein in the tumour. Using mouse models, Terzian et al. recently showed that this accumulation of mutant p53 protein is not associated with specific properties of the protein itself but instead depends on the endogenous genetic background of the tumours and on two important genes, mouse double minute 2 (Mdm2) and the cyclin kinase inhibitor p16INK4a. Mice expressing mutant p53 in the absence of Mdm2 display more aggressive metastatic tumours. In light of these observations, targeting the MDM2-p53 interaction for therapy of human cancer could be more complicated than previously anticipated.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mutation, Missense*
  • Neoplasms* / diagnosis
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation


  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Mtbp protein, mouse
  • Tumor Suppressor Protein p53