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What is p53 ?
After the identification of the p53 protein and the subsequent cloning of p53 genes from several species, early observations suggested that p53 may function as an oncogene, because overexpression of p53 appeared to cause oncogenic transformation of cells. In the late 1980s, however, several critical discoveries defined the normal function of p53 to be anti-oncogenic. Wild-type p53 genes, when introduced into cells, were found to be growth suppressive. The screening of DNA from colon cancer patients revealed that p53 mutations occur with unusually high frequency in tumor tissue, an observation that was extended to most of the other major forms of human cancer. Indeed, members of Li-Fraumeni cancer-prone families were shown to carry germ-line p53 mutations. The importance of these observations was underscored by the finding that mice that are homozygous null for p53, although developmentally competent, are highly predisposed to tumors.
The functional character of the p53 protein was determined by experiments showing that p53 contains a strong transcriptional activation domain within its amino terminus and that it is a tetrameric, sequence-specific DNA-biding protein with a defined cognate binding site containing two copies of the 10-mer (5'-RRRCA/TT/AGYYY-3'). Although the p53 protein acts as a transcriptional activator of genes ...