p53 as a tumor suppressor
The p53 gene codes for the formation of p53 protein, through the process known as translation. It is now common to designate the gene as TP53, and the protein as p53. The newly formed p53 protein is unstable and present in low levels under normal conditions. However, when the cell is confronted by stress, such as ultraviolet damage, ionizing radiation or oncogene activation, p53 is stabilized by the addition of certain chemical groups and increases in concentration. 1 Due to its essential role as a tumor suppressor, p53 has been called the "guardian of the genome." It can be thought of as continuously monitoring the integrity of the DNA molecule, and when defects are found to take steps to either correct the errors or destroy the cell.
When changes in the DNA are detected, p53 protein binds to a gene to promote the transcription of another protein, p21. This protein, in turn, enters the metabolic process of the cell to shut down the cell cycle at the G1 or growth phase. 4 This would allow time to repair the DNA just before it enters the DNA replication phase. If this repair were possible, it would reduce the possibility of mutations and progression towards cancer. If repair is not possible, p53 stimulates the cell to enter a pathway leading to apoptosis, or programmed cell death. In total, p53 targets around 150 genes to prevent proliferation of damaged cells.
p53 as an oncogene
The p53 gene appears to be very subject to mutation. Most mutations occur in the DNA-binding region of the gene. The resultant protein has an abnormal structure and cannot function. With the DNA structure now unprotected against defects, mutations can accumulate, checks and balances on the cell cycle can fail to operate, and cell growth can proceed unchecked.
The MDM2 molecule plays a normal regulatory role by removing p53 from the cell when it is no longer needed. A particular oncogene, however, over activates MDM2 through an enzyme so that the concentration of p53 remains greatly depleted.
Treatment approaches based on restoring p53 function
