Tumor Protein 53 (p53) is a transcription factor that is known to function as a tumor suppressor. p53 controls the cell cycle, by arresting growth either before DNA replication in the G1 phase or before mitosis in the G2 phase of the cell cycle. It has recently been shown that the p53 signal transduction network is actually inactive or poorly active in normal cells. Ubiquitination and subsequent degradation of the transcribed p53 also keeps its level in check in normal cells. However, the gene is activated by stress signals, such as carcinogen-induced DNA damage, abnormal proliferative signals, hypoxia, or loss of cell adhesion. In addition, under the influence of such stress signals, the ubiquitin dependent degeneration of the protein is also affected, resulting in a high concentration of the protein within the cell.
The p53 protein binds to promoters of a number of specific genes as a transcription factor, and thereby, initiates their transcription. Most of the genes transcribed fall under one of the following categories: genes involved in controlling the cell cycle (p21 WAF1/CIP1, WIP1, EGFR, and other Cyclins), genes involved in DNA repair (GADD45, PCNA), genes involved in angiogenesis (TSP-1, BAI1), and genes involved in cellular stress response (TP53TG1, CSR, PIG3). Through the transcription of these proteins, p53 is able to play an important role in the processes of prevention of tumor development, inhibition of abnormal growth of cells, DNA repair, and inhibition of angiogenesis.
The role of the p53 protein in tumor suppression is clearly demonstrated by mutations in the gene. Mutations in one copy of the gene may lead to a disease known as Li-Fraumeni Syndrome, characterized by a propensity to develop tumors in early adulthood. Interestingly, more than 50% of human tumors have been found to contain a mutation or deletion in the p53 gene.