p53 Peptides
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Introduction
p53 peptides is a tumor suppressor gene, located in human chromosome 17p13.1, it is a nuclear phosphorylated protein composed of 393 amino acids with a molecular weight of 53kD. p53 peptides is mainly distributed in nuclear cytoplasm and can bind specifically to DNA. Its activity is regulated by phosphorylation, acetylation, methylation, ubiquitin and other post-translational modifications. p53 gene is a negative regulatory factor in cell growth cycle, which is related to cell cycle regulation, DNA repair, cell differentiation, apoptosis and other important biological functions. p53 peptides is an important anticancer gene, its wild-type causes cancer cell apoptosis, thus preventing canceration, and it also has the function of helping cells repair defects. The mutation type of p53 can increase canceration.
Mechanism of action
The interaction of p53 peptides with other peptides and p53 gene mutation can lead to the loss of normal biological function. The biochemical activity of p53 peptides may also be regulated by interaction of the C-terminus with single stranded RNA or DNA. The activity of p53 peptides most tightly linked to its tumor suppressor activity is the ability of the protein to bind to DNA sequence-specifically. Inactivating point mutations usually map within the active site for sequence specific DNA binding or within the central core DNA binding domain. Thus, sequence-specific DNA binding is a biologically relevant function of p53 peptides, and understanding its regulation may reveal mechanisms whereby the cell regulates a key damage-responsive pathway. The biological function of normal p53 peptides is similar to that of “genome guard (guardian of the genome)”. The damage site of DNA is examined in G1 phase to monitor the integrity of genome. In case of injury, p53 peptides blocks DNA replication to provide sufficient time for DNA repair, and if repair fails, p53 protein induces apoptosis. If both copies of p53 gene are mutated, they lose control of cell proliferation and lead to cell carcinogenesis.
Application of p53 Peptides
p53 peptides is a central feature in a variety of pathological situations, such as liver cancer, breast cancer, bladder cancer, gastric cancer, prostate cancer, etc. Studies have shown that p53 overexpression is associated with metastasis, recurrence and poor prognosis, so further understanding the basic biological mechanism of p53 is very important for future clinical application.
References
- Hupp, T. R., Sparks, A., Lane, D. P., (1995). Small Peptides Activate the Latent Sequence-Specific DNA Binding Function of p53. Cell, 83, 237-245.
- Tyler, A. F., Korsmeyer, S. J., Bernal, F., Korsmeyer, S. J., Walensky, L. D., Verdine, G. L., (2007). Reactivation of the p53 Tumor Suppressor Pathway by a Stapled p53 Peptide. Journal of the American Chemical Society, 129(9), 2456-2457.
