p53 is a short-lived, non-abundant protein that regulates the response of cells to DNA damage, in part through transcriptional activation of genes involved in cell cycle control, DNA repair, and apoptosis. p53 is a tumor suppressor protein; consequently, mice in which the p53 gene has been disrupted develop tumors with high frequency, and deletions or mutations in the p53 gene are prevalent in a majority of human cancers. The protein level and activity of p53 are regulated, and this is accomplished by MDM2 (murine double minute 2). The MDM2 gene is induced by p53, and MDM2 prevents apoptosis by inhibiting p53 activity and promoting its degradation.
In response to DNA damage, the p53 protein is phosphorylated on each of the seven serines and one threonine the in the first 50 amino acids of its N-terminal transactivation domain as well as at several sites in its C-terminal tetramerization/regulatory domain. As a transcription factor, p53 induces or represses several genes that regulate cell cycle arrest, DNA repair or apoptosis, including p21WAF1, MDM2, GADD45, p53R2, and p53AIP1. Recent studies suggest that specific p53 phosphorylation events are important for the activation or repression of specific promoters.