Regulation of p53 in response to DNA damage

Oncogene. 1999 Dec 13;18(53):7644-55. doi: 10.1038/sj.onc.1203015.


Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS). Under normal conditions, p53 levels are maintained at a low state by virtue of the extremely short-half life of the polypeptide. In addition to this, p53 normally exists in an largely inactive state that is relatively inefficient at binding to DNA and activating transcription. Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair. Recent work has suggested that this regulation is brought about largely through DNA damage triggering a series of phosphorylation, de-phosphorylation and acetylation events on the p53 polypeptide. Here, we discuss the nature of these modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / metabolism
  • DNA Damage / genetics
  • DNA Damage / physiology*
  • DNA Helicases / metabolism
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Humans
  • Nuclear Proteins*
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2
  • Saccharomyces cerevisiae Proteins
  • Signal Transduction
  • Trans-Activators / metabolism
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein Serine-Threonine Kinases
  • Adenosine Triphosphatases
  • Rad3 protein, S cerevisiae
  • DNA Helicases