What is p53 and why does a loss of function mutation at p53 leads to cancer or uncontrolled cell growth?
In most cases, the p53 gene is mutated, giving rise to a stable mutant protein whose accumulation is regarded as a hallmark of cancer cells. Mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions that endow cells with growth and survival advantages.
How does p53 become mutated?
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 cancer is p53 associated with?
P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers.
Is p53 always active?
Besides its primary function as a transcription factor, p53 can also promote apoptosis through direct interaction with proapoptotic and antiapoptotic proteins . The activity of p53 is always under tight control, which ensures that it is not overly abundant in nonstressed cells.
What does p53 positive mean?
found that p53 expression, defined as a single cancer cell with positive p53 staining, was significantly correlated with large tumor size and negative ER/PgR status, and was a prognostic indicator of OS and failure-free survival in early-stage breast cancer (19).
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 the p53 protein work?
The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way.
What happens when p53 is overexpressed?
Our research showed that was a significant inverse correlation between p53 overexpression and response to chemotherapy and a stronger association between high P53 overexpression (%) and a genetic mutation of p53 (p=0.0001). More than 50% overexpression indicated a strong probability of genetic mutation.
Is p53 associated with hereditary cancers?
LFS is a hereditary genetic condition. This means that the cancer risk can be passed from generation to generation in a family. This condition is most commonly caused by a mutation (alteration) in a gene called TP53, which is the genetic blueprint for a protein called p53.
Do cancer cells have p53?
Since over 50% of human cancers carry loss of function mutations in p53 gene, p53 has been considered to be one of the classical type tumor suppressors. Mutant p53 acts as the dominant-negative inhibitor toward wild-type p53. Indeed, mutant p53 has an oncogenic potential.
Is p53 good or bad?
p53 Germline Mutations and Li–Fraumeni Disease. p53, famously dubbed ‘The Guardian of the Genome’, is arguably the most significant gene for cancer suppression. Somatic loss of function of p53 underpins tumor progression in most epithelial cancers and many others besides.