Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body. These changes have been found in a genetic condition called Li-Fraumeni syndrome and in many types of cancer.
What causes p53 to mutate?
The TP53 gene may be damaged (mutated) by cancer-causing substances in the environment (carcinogens) such as tobacco smoke, ultraviolet light, and the chemical aristolochic acid (with bladder cancer). Often times, however, the toxin leading to the mutation is unknown.
What proteins does p53 activate?
It is clear that p53 activates several downstream targets responsible for inducing cell cycle arrest, including GADD45, Reprimo, p21, and 14-3-3σ 54, 55. p53 has even been recently shown to induce microRNA expression as an additional mechanism for activating cell cycle arrest 56.
How is p53 mutation detected?
Methods used for the detection of P53 mutations are based either on genomic DNA or mRNA as a template (11,12,15). The most widely used methods are based on DNA sequencing. However, few studies exist that compare sequencing assays by using both RNA and DNA targets (18–22).
What happens if both p53 alleles are mutated?
These mutations result in an altered p53 protein that cannot regulate cell proliferation effectively and is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to the growth of tumors.
How does p53 detect DNA damage?
After UV-induced DNA damage, activated p53 induces the expression of p48 and XPC, thus increasing the cell’s capacity to locate and target DNA damage for repair.
What is a p53 mutation?
TP53 gene mutations change single amino acids in p53, which impair the protein’s function. Without functioning p53, cell proliferation is not regulated effectively and DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to tumor growth.
How is p53 mutation treated?
Reactivating p53 with Drugs Another experimental cancer therapy in development involves “patching” mutated p53 genes in cells so they can function normally again. Doctors could potentially use this medicine to treat cancer and prevent it by repairing defective p53 genes before cells have the chance to become cancerous.
How does p53 become activated?
The tumour suppressor protein p53 is stabilised and activated in response to ionising radiation. This is known to depend on the kinase ATM; recent results suggest ATM acts via the downstream kinase Chk2/hCds1, which stabilises p53 at least in part by direct phosphorylation of residue serine 20.
What does p53 do when it is activated?
Upon activation, p53 induces the expression of a variety of gene products, which cause either a prolonged cell-cycle arrest in G1, thereby preventing proliferation of damaged cells, or apoptosis, thereby removing damaged cells from our body.
How common is p53 mutation?
The p53 gene contains homozygous mutations in ~50–60% of human cancers. About 90% of these mutations encode missense mutant proteins that span ~190 different codons localized in the DNA-binding domain of the gene and protein.
What is a p53 gene mutation?
