p53

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The p53 protein is encoded by the tumor suppressor gene p53, which plays an important role in regulating the cell cycle, inducing inducing apoptosis and activating DNA repair. Human p53 gene is located in chromosome 17p13.1, and contains 11 exons and 10 introns, encoding 393 amino acids. The p53 protein is a nuclear phosphorylated protein with a synthetic relative molecular weight o of 43.7 kDa. But because the protein fragment appears at 53 kDa indicated by markers, it is named as p53.

The primary structure partition of p53 protein:

As a transcription factor, p53 protein act its functions in the nucleus relying on nuclear localization signals. Nuclear export signals can mediate the p53 protein shuttle from the nucleus to the cytoplasm. X-ray diffraction shows that the p53 protein has two α-helices and 11 beta sheets. The p53 monomers form active tetramers through the above-mentioned interactions.

Under normal circumstances, the p53 gene exists in the cell in the form of wild type (Wild type p53, wt-p53), and the generated p53 protein will be rapidly degraded by oncogenes murine represented by double minute 2 (MDM2). So p53 protein levels are low, and difficult to accumulate to detectable amounts for immunohistochemical analysis. When the p53 gene is mutated, it becomes mutant p53 (mt-p53), which can change its encoded p53 protein in configuration. Such change in configuration increases the stability of p53 protein, thus makes it unable to degrade and accumulate in cells, which can be detected by immunohistochemical methods. The mutations of amino and carboxyl terminals of p53 protein generally do not cause functional changes, but can affect the formation of tetramers. By contrast, mutations in the central core region can easily cause loss of p53 function. Since the accumulation of p53 protein in tissues and the mutation of p53 gene is highly correlated, p53 protein is detected by immunohistochemistry in clinical to indicate the mutation of p53 gene, so as to evaluate the risk of cancer and the prognosis of cancer patients.

Reference

[1]Kato S, Han S Y, Liu W, et al. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis[J]. PNAS, 2003, 100(14): 8424- 8429.
[2]Zhang Y, Xiong Y. A p53 amino-terminal nuclear export signal inhibited by DNA damage induced phosphorylationl[J]. Science, 2001, 292(5523):1910- 1915.
[3]Achison M, Hupp T R. Hypoxia attenuates the p53 response to cellular damage[J]. Oncogene, 2003, 22(22): 3431-3440.