Divorcing ARF and p53: an unsettled case

Nat Rev Cancer. 2006 Sep;6(9):663-73. doi: 10.1038/nrc1954. Epub 2006 Aug 17.


Mammalian cells that sustain oncogenic insults can invoke defensive programmes that either halt their division or trigger their apoptosis, but these countermeasures must be finely tuned to discriminate between physiological and potentially harmful growth-promoting states. By functioning specifically to oppose abnormally prolonged and sustained proliferative signals produced by activated oncogenes, the ARF tumour suppressor antagonizes functions of MDM2 to induce protective responses that depend on the p53 transcription factor and its many target genes. However, ARF has been reported to physically associate with proteins other than MDM2 and to have p53-independent activities, most of which remain controversial and poorly understood.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
  • Signal Transduction
  • Tumor Suppressor Protein p14ARF / physiology*
  • Tumor Suppressor Protein p53 / physiology*


  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-mdm2