p53 is a tumor suppressor protein, also known as "Guardian of the Genome". It plays an important role in cell cycle control and apoptosis. Defective p53 could allow abnormal cells to proliferate, resulting in cancer. As many as 50% of all human tumors contain p53 mutants.
In normal cells, the p53 protein level is low. DNA damage and other stress signals may trigger the increase of p53 proteins, which have three major functions: growth arrest, DNA repair and apoptosis (cell death). The growth arrest stops the progression of cell cycle, preventing replication of damaged DNA. During the growth arrest, p53 may activate the transcription of proteins involved in DNA repair. Apoptosis is the "last resort" to avoid proliferation of cells containing abnormal DNA.
The cellular concentration of p53 must be tightly regulated. While it can suppress tumors, high level of p53 may accelerate the aging process by excessive apoptosis. The major regulator of p53 is Mdm2, which can trigger the degradation of p53 by the ubiquitin system.
p53 is a transcriptional activator, regulating the expression of Mdm2 (for its own regulation) and the genes involved in growth arrest, DNA repair and apoptosis. Some important examples are listed below.
Regulation of p53
As mentioned above, p53 is mainly regulated by Mdm2. The regulation mechanism is illustrated in the following figure.
Roles of p53
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.