TP53 (gene)

TP53 is a tumor suppressor gene that is named after, and provides instructions for making, a protein called tumor protein 53 (TP53). Through the effect of the protein that it produces, TP53 is a tumor suppressor gene, which means that it regulates the cycle of cell division by keeping cells from growing and dividing too fast or in an uncontrolled way.

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The p53 tumor protein is located in the nucleus of cells throughout the body and can bind directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the cell will undergo programmed cell death (apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, the p53 tumor protein prevents the cell from dividing and signals it to undergo apoptosis. This process prevents cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.

Because the p53 tumor protein is essential for regulating cell division, it has been nicknamed the "guardian of the genome."

The human TP53 gene is located on the short (p) arm of chromosome 17 at position 13.1, from base pair 7,512,463 to base pair 7,531,641.

Related conditions

Bladder cancer: Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. Somatic mutations in the TP53 gene have been found in some cases of bladder cancer. Most of these mutations replace one amino acid (a building block of proteins) with another amino acid in the p53 tumor protein. The altered protein cannot bind to DNA correctly, which prevents the protein from effectively regulating cell growth and division. As a result, DNA damage accumulates in cells and they divide in an uncontrolled way, leading to a cancerous tumor. Mutations in the TP53 gene may also help predict whether bladder cancer will progress and spread to nearby tissues and whether the disease will recur after treatment.

Li-Fraumeni syndrome: More than 55 different inherited mutations in the TP53 gene have been found in individuals with Li-Fraumeni syndrome. Many of these changes involve the substitution of one amino acid for another amino acid in the part of p53 tumor protein that binds to DNA. Other types of mutations include deletions of small amounts of DNA within the gene. Mutations in the TP53 gene lead to a version of the p53 tumor protein that cannot regulate cell growth and division. The altered protein is unable to signal cells with mutated or damaged DNA to undergo apoptosis. As a result, such cells continue to divide and can form tumors.

Other cancers: Somatic mutations in the TP53 gene are the most common genetic changes found in human cancer, occurring in about half of all cancers. For example, TP53 gene mutations have been identified in several types of brain tumor, a type of bone cancer called osteosarcoma, a cancer of muscle tissue called rhabdomyosarcoma, and adrenocortical carcinoma (a cancer of the outer layer of the adrenal glands, which are small glands located on top of each kidney). DFSP (dermatofibrosarcoma protuberans)may also be linked to a P53 mutation. Most TP53 gene mutations substitute one amino acid for another in the p53 tumor protein, which leads to the production of an altered version of the protein that cannot effectively bind to DNA. This altered protein can build up in nuclei of cells, preventing the cells from undergoing apoptosis in response to DNA damage. Instead, these damaged cells continue to grow and divide in an unregulated way, which can lead to cancerous tumors.

References

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