A tumor suppressor gene like P53 is there, to stop the formation of tumors. It is considered that all those, who inherit only one functional copy of the p53 gene from their parents, are more likely to become a prey of cancer as they are predisposed to cancer. They usually develop several independent tumors in a variety of tissues in early adulthood. Such condition is known as Li-Fraumeni syndrome but it is quit rare.
By having a deep look at the genes positioning map, p53 gene can be found on chromosome 17. p53 protein binds DNA, inside a cell, which in turn stimulates another gene to produce a protein called p21. P21 further interacts with a cell division-stimulating protein. As a result, the cell cannot pass through to the next stage of cell division. Mutant p53 can no longer bind DNA in a way, it should be and as a consequence the p21 protein is not made available to act as the ‘stop signal’ for cell division. Thus cells divide uncontrollably, and form tumors.
The molecular mechanisms of cancerous growth has come from the use of mice which has taken as models for human cancer, in which powerful ‘gene knockout’ techniques did used. The amount of information that exists on all aspects of p53 normal function and mutant expression in human cancers is now vast, reflecting its key role in the pathogenesis of human cancers. p53 is considered as just one component of a network of events that take part in tumor formation.
Role of P53 Gene in Cancer
Here you can read about the role of P53 Gene in Cancer, P53 protein role in cell regulation and further relevant information.
Role of the P53 Protein in the Cell Cycle
In terms of cell cycle, p53 protein plays an integral role in the cell. It is normally present in all cell types. As we know that protein is always localized in the nucleus and functions as a transcription factor. Besides all other proteins, p53 protein is at the center of a large network that monitor the health of a cell and cellular DNA. It plays following important roles in cell cycle:
- The p53 protein is the conductor of a well orchestrated system of cellular damage detection and control. As soon as the protein network sense the damage, p53 protein aids in the decision between repair and the induction of cell death. This process is called apoptosis.
- As a transcription factor, p53 stimulates the transcription of a group of target genes. Among target genes, p21 is one of the most important. The product of the the p21 gene is a negative regulator of cyclin-dependent kinases, enzymes that are critical in the progression of the cell cycle and ultimately cell division.
- By stimulating the transcription of the p21 gene, p53 prevents cell proliferation and leads towards cell repairs, if possible. In case of irreparable damage, the p53 protein can help to trigger cell death.
- All cancer cells contain mutations in combinations of tumor suppressors and oncogenes. The removal of functional p53, the ‘guardian of the genome,’ from a cell allows for the accumulation of even more DNA damage and the division of cells that contain damaged DNA.
What is a Tumor Suppressor Protein?
A gene named as retinoblastoma gene encodes a protein that acts by altering the activity of transcription factors. By interacting with transcription factors, Rb is able to indirectly control gene expression. Ultimately, Rb and its relatives contribute to the control of the cell division process. The Rb gene is mutated in many types of cancer. Two different forms of retinoblastoma have been differentiated.
- The sporadic form of the disease can affect anyone. It is always dependent on mutations or genetic changes, that occur during the lifetime of the affected individual
- The familial form is found in individuals, who inherit a defective copy of the gene from one of their parents.
In the presence of other tumor suppressors, the cancer phenotype is not apparent unless both copies of the gene are damaged. Individuals with the inherited form of the disease often suffer from many different cancerous growths, especially osteosarcomas. In addition to this, there are many other types of cancer associated with Rb mutation such as lung, breast, and bladder carcinomasIs.
P53 Oncogene or a Suppressor Gene?
When the p53 gene become mutated, it gives rise to a stable mutant protein whose accumulation is regarded as a hallmark of cancer cells. These mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions As a result, cells become abnormal in terms of growth and survival advantages.
Mutation in the P53 Gene
P53 gene mutation have several different effects on the activity of the gene, depending on the location of the alteration.
- Mutations can occur in regulatory regions also called promoter, that basically control how often, and when, the gene is transcribed. Here mutation can result in a decrease or absence of p53 in the cell.
- Mutations that occur in the protein coding region of the gene can impact the expression of the gene in several ways like it may cause slow activity of p53 as a transcription factor. In addition, it can cause changes in p53 that make it more susceptible to degradation.