TP53
TP53, also known as tumor protein p53, is a gene that plays a critical role in regulating the cell cycle and thus functions as a tumor suppressor. It is pivotal in preventing cancer formation, making it one of the most studied genes in medical research. The protein encoded by the TP53 gene is involved in preventing cancer by maintaining the stability of the genome through the repair of DNA, initiating apoptosis in the case of DNA damage that cannot be repaired, and halting the cell cycle to allow for DNA repair. Mutations in TP53 are found in approximately half of all cancers, underscoring its importance in cancer biology.
Function[edit | edit source]
The TP53 gene encodes for the p53 protein, which acts as a transcription factor regulating the expression of a wide array of genes involved in cell cycle arrest, apoptosis, senescence, DNA repair, and changes in metabolism. Upon cellular stress, such as DNA damage, oxidative stress, or oncogene activation, p53 is activated and can induce cell cycle arrest at the G1/S checkpoint, allowing the cell time to repair DNA damage before proceeding to DNA synthesis. If the damage is irreparable, p53 can initiate programmed cell death (apoptosis) to prevent the propagation of the damaged DNA. This mechanism is crucial for maintaining genomic stability and preventing oncogenesis.
Mutation and Cancer[edit | edit source]
Mutations in the TP53 gene are the most common genetic alterations observed in human cancers. These mutations can lead to the production of a malfunctioning p53 protein that cannot effectively perform its role in DNA repair or apoptosis, allowing cells with damaged DNA to proliferate and form tumors. Mutant p53 can also gain oncogenic functions, actively promoting cancer progression. The loss of effective p53 function is considered a key step in the development of many types of cancer.
Clinical Significance[edit | edit source]
Given its central role in cell cycle regulation and apoptosis, TP53 is a significant focus of cancer research. Therapeutic strategies aimed at restoring normal p53 function in tumors are being explored, including gene therapy to replace the mutated TP53 gene and drugs designed to restore the normal function of mutated p53 protein. Additionally, the status of TP53 mutation is used as a prognostic marker in various cancers, as it often correlates with a more aggressive disease and poorer prognosis.
Genetic Testing[edit | edit source]
Genetic testing for TP53 mutations is available and can be particularly important for individuals with a family history of cancers associated with Li-Fraumeni syndrome, a rare disorder that greatly increases the risk of developing several types of cancer. This syndrome is often caused by inherited mutations in the TP53 gene.
See Also[edit | edit source]
References[edit | edit source]
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Contributors: Prab R. Tumpati, MD