Reciprocal down-regulation of p53 and SOD2 gene expression - implication in p53 mediated apoptosis

p53 regulates the transcription of a number of genes among which are differ ent redox-related genes. It has been proposed that these genes can induce a cellular oxidative stress leading to p53-dependent apoptosis (Polyak er al ., 1997). MnSOD, the product of superoxide dismutase 2 (SOD2) gene, is one of the major cellular defences against oxidative stress. We demonstrate her e that p53 is able to repress SOD2 gene expression and that this repression takes place at promoter level. We show the importance of this regulation f or the p53 function, by demonstrating that an overexpression of MnSOD decre ases p53-mediated induction of apoptosis. Moreover, we demonstrate that MnS OD overexpression decreases p53-gene expression at the promoter level. Thes e findings raise the hypothesis that p53 and SOD2 genes are mutually regula ted leading to the modulation of various cellular processes including apopt osis.