p53, also known as TP53 or tumor protein (EC :2.7.1.37) is a gene that codes for a protein that regulates the cell cycle and hence functions as a tumor suppression. It is very important for cells in multicellular organisms to suppress cancer. P53 has been described as "the guardian of the genome", referring to its role in conserving stability by preventing genome mutation (Strachan and Read, 1999). The name is due to its molecular mass: it is in the 53 kilodalton fraction of cell proteins.

The p53 protein is a phosphoprotein made of 393 amino acids. It consists of four units (or domains):

A domain that activates transcription factors.

A domain that recognizes specific DNA sequences (core domain).

A domain that is responsible for the tetramerization of the protein.

A domain that recognized damaged DNA, such as misaligned base pairs or single-stranded DNA.

Wild-type p53 is a labile protein, comprising folded and unstructured regions which function in a synergistic manner (Bell et al. 2002).p53 protein has been voted molecule of the year.

The  roles of p53 in growth arrest and apoptosis are illustrated in Figure 4-H-6. p53 is also directly involved in DNA repair.  One of its transcriptional target gene, p53R2, encodes ribonucleotide reductase, which is important for both DNA replication and repair.  p53 also interacts directly with AP endonuclease and DNA polymerase which are involved in base excision repair.

If the p53 gene is damaged, tumor suppression is severely reduced. People who inherit only one functional copy of p53 will most likely develop tumors in early adulthood, a disease known as Li-Fraumeni syndrome. p53 can also be damaged in cells by mutagens (chemicals, radiation or viruses), increasing the likelihood that the cell will begin uncontrolled division. More than 50 percent of human tumors contain a mutation or deletion of the p53 gene.

In health p53 is continually produced and degraded in the cell. The degradation of p53 is, as mentioned, associated with MDM-2 binding. In a negative feedback loop MDM-2 is itself induced by p53. However mutant p53s often don't induce MDM-2, and are thus able to accumulate at very high concentrations. Worse, mutant p53 protein itself can inhibit normal p53 (Blagosklonny, 2002).