P53 Tumor Suppressor Gene
Cells undergo a natural cycle of division, growth and death. Damage to the DNA in the cell nucleus may disrupt this process, resulting in cancerous cells that grow and divide too quickly. Healthy cells also contain genes that halt the process when abnormal growth is detected. If these tumor suppressor genes are damaged, however, the cell loses its ability to stop the cancer growth.
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Biology of Cancer
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Uncontrolled growth defines cancer cells Unlike healthy cells, cancer cells can override the normal controls regulating growth, division and natural cell death, or apoptosis, according to the American Cancer Society. As cancer cells continue to grow and reproduce, they accumulate into tumors.
Tumor Suppressor Genes
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The body naturally produces genes that stop cells from dividing if they show signs of abnormal behavior. These tumor suppressor genes produce proteins that freeze cells in a resting phase, halting the process of division and shutting down tumor growth, according to Kimball's Biology. Mutations or defects in tumor suppressor genes impair the production of the proper proteins and cancer cell growth proceeds uninterrupted. Mutations of the tumor suppressor gene labeled p53 is found in more than half of all cancers, according to Kimball's Biology.
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Mechanism of p53
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The p53 gene is composed of four chains arranged in a star, according to David S. Goodsell, PhD, in an article in The Oncologist. An activation domain at the tip of each arm activates expression of the gene. The arms meet in the center in a knot-like formation that binds to the target site. The p53 binds to the defective DNA, which stimulates production of a protein called p21, according to the National Institutes of Health. The p21 protein attaches to a third protein, cell-division stimulating protein. When joined, the two proteins freeze the cell and prevent it from dividing. In cases where the DNA defect is severe, p53 triggers the process of apoptosis or cell death.
P53 Activity in Cancer
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Most mutations in the p53 gene that result in cancer occur at the center binding domain. Mutated p53 is unable to bind to the DNA, according to the NIH. Because the initial binding process is impaired, the cell fails to produce the p21 necessary to halt the process of cell division. Without a mechanism to stop the defective cell from reproducing, the cancer grows. One minute alteration in the amino acid sequence is enough to deactivate p53, according to Goodsell. The altered chemical makeup of the gene distorts the signals from p53 and the consequent protein cascade.
Treatment Implications
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Because mutations in p53 are common in many cancers, repairing these mutations is a focus of research, according to the ACS. Early laboratory studies inserted normally functioning p53 genes into viruses that were then inserted into cancer cells. Cancer cells infected with the p53-loaded viruses grew slower than uninfected cancer cells. Unfortunately, the overall results of the experiment were considered a failure and further studies with the loaded viruses were discontinued.
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