THE TUMOR-SUPPRESSOR GENE P53 - FUNCTION AND SIGNIFICANCE IN GASTROENTEROLOGY

The p53 gene is a tumor suppressor gene. The encoded p53 protein direc tly induces the expression of genes that are involved in cell cycle re gulation. p53 was named guardian of the genome for its prevention of a n otherwise fatal outcome under DNA damaging conditions. Under these c onditions p53 inhibits cell cycle progression or induces apoptosis. Th e p53 protein has been structurally and functionally divided into four domains, two of which are of crucial importance: The sequence specifi c DNA-binding domain and the aminoterminal transactivation domain. The y are both required to trigger the downstream processes following p53 expression. Mutations and inactivation of p53 by oncogenes are frequen t events in the development of human neoplasia. That includes gastroin testinal tumors with their mutational spectra reflecting tissue-specif ic, influences of endogenous and exogenous factors in carcinogenesis. Despite considerable progress in molecular biology, clinical applicabi lity of p53 in both diagnostic and therapeutic strategies has not yet been validated.