Figure 1. p53 activity in normal cells. Wild-type p53 binds to the promoter of a wide variety of genes and causes their increased transcription. One of these genes encodes the protein MDM2, which can bind to p53; this subsequently increases the rate of ubiquitin-mediated degradation of p53, resulting in p53 having a short half-life. After chemotherapeutic agents induce DNA damage in cells, there is reduced binding of MDM2 to p53, p53 levels are increased as a result of the increased half-life, and there is increased transcription of p53-dependent genes such as p21 (encoding the cyclin-dependent kinase inhibitor p21CIP1/WAF1) and gadd45 (for ‘growth arrest and DNA-damage-inducible’). Depending on the cellular context, this can lead to cell-cycle arrest and/or apoptosis.
