What is the main function of p53?
The p53 protein is a key cell cycle regulator that manages the response to stress signals either by inducing cell growth arrest, senescence or apoptosis. The nature and intensity of stress signal, the cell type, and the cellular context dictate the final outcome.
Why is p53 high in cancer cells?
It is well known that the p53 protein may induce cell apoptosis and regulate cell proliferation. Mutation of the p53 gene results in the loss of its ability to induce cell death, which leads to uncontrolled cell growth, thus, promoting tumorigenesis (6,7).
What is the relationship between p53 and cancer?
p53 is a nuclear transcription factor with a pro-apoptotic function. 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.
Why is the p53 gene important to cancer research?
The TP53 gene is mutated in around 50% of cancer cells, but in addition to its role in tumor suppression, cancer cells themselves can find ways to inactivate and alter the gene, leading to new functions that help sustain the growth of a cancer.
What cancers is p53 associated with?
P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers. Environ Health Perspect.
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.
How do cancer cells inactivate p53?
Various mechanisms inactivate p53 in cancer, including point mutations resulting in synthesis of an inactive mutant protein, deletion of the total gene or its portion, damage to the genes involved in regulating the p53 activity, and defects in p53 target genes.
How is p53 inactivated in cancer?
The p53 protein is such a powerful tumor suppressor that it is inactivated in almost every tumor, through either mutations in the TP53 gene or deregulation of its associated pathways.
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.
Is p53 mutated in all cancers?
Indeed, TP53 mutations were reported to occur in almost every type of cancer at rates varying between 10% (e.g., in hematopoietic malignancies7) and close to 100% (e.g., in high-grade serous carcinoma of the ovary8).
Do all cancers have 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 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).