The p53 (or TP53) gene was discovered in 1979 and has emerged as one of the most important cancer-related genes to date. The gene, located on chromosome 17, produces a protein product that functions as a transcription factor . The genes controlled by p53 are involved in cell division and viability. Like the other tumor suppressors, the p53 protein functions to prevent unregulated cell growth.
The p53 protein interacts directly with DNA. It also interacts with other proteins that direct cellular actions. When DNA damage or other cellular insults are detected, p53 has the power to trigger cell death or apoptosis. The crucial role of p53 in maintaining proper control of cellular processes is underscored by the fact that the p53 gene is found to be defective in about half of all tumors, regardless of their type or origin.12 The mutations that inactivate p53 may be acquired during the lifespan of an individual (sporadic mutations) or they may be inherited. transcription.
A Closer Look at the Discovery of p53 Gene
In 1979, scientists discovered a novel protein. This protein, which could bind to a transforming protein (Large T antigen) from Simian Virus 40 (SV40), was more prevalent in cells transformed (immortalized and made potentially tumorigenic) by this virus than in normal cells. The protein and its corresponding gene were named p53, in reference to the mass of the protein (53 kilodaltons). The p53 gene is located on chromosome 17 at position p13.3
Although p53 was the second tumor suppressor to be discovered (after Rb), scientists did not understand its true role in the cell until ten years after its discovery.1 Because p53 was present at increased levels in transformed cells, researchers first believed that it acted as an oncogene.4 This belief was supported by initial research. Scientists found that when the p53 gene was transferred into cells, the cells underwent transformation. However, researchers later discovered that the p53 gene that had been transferred was in fact a mutant form of the gene. One normal function of the p53 gene is to prevent cell transformation!41
Several lines of evidence have lead to the conclusion that this gene is a tumor suppressor. Since 1989, research into p53 has made steady progress. The protein has been found to be involved in numerous cellular processes. However, there is still debate regarding the feasibility of using p53 as a clinical tool, such as its use in identifying cancerous cells.5 Some current research efforts are designed to test the feasibiltiy of clinical treatments that can repair the gene or replace it when it becomes damaged.6
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- 2. Introgen [http://www.introgen.com/infotp.html]
- 3. "Atlas of Genetics and Cytogenetics in Oncology and Haematology." (2002) [http://www.infobiogen.fr/services/chromcancer/Genes/P53ID88.html]
- 4. a. b. Vogelstein B, Kinzler KW. "Achilles' heel of cancer?" Nature (2001). 412(6850): 865-866. [PUBMED]
- 5. Soussi T. "The p53 tumor suppresor gene: from molecular biology to clinical investigation." Annals of the New York Academy of Sciences (June 2000). 910: 121-139. [PUBMED]
- 6. Fighting Cancer with Biotechnology. [http://www.biotechinstitute.org]