The Role of the p53 Protein in the Apoptotic Response

When mammalian cells or tissues are exposed to DNA damaging agents a programmed cell death pathway is induced as well as a cell cycle arrest. In mice in which the p53 gene has been inactivated by homologous recombination this response is profoundly diminished. These mice develop normally so that developmentally induced apoptotic events do not require p53. The p53 gene product is a 393 amino acid nuclear protein that binds specifically to DNA and can act as a positive transcription factor. High levels of p53 can induce the transcription of gene products involved in the cell cycle arrest and apoptotic pathway. The p53 proteins activity is very tightly controlled both by allosteric regulation of its DNA binding function and by regulation of the protein's stability. These results are discussed in the context of the mutations in p53 found in human tumours and their implications for the treatment of the disease by the use of radiation and chemotherapeutic agents that target DNA.