Related Experiment Videos
Reciprocal down-regulation of p53 and SOD2 gene expression-implication in p53 mediated apoptosis
P Drane1, A Bravard, V Bouvard
1Commissariat à l'Energie Atomique (CEA), Laboratoire de Cancérogenèse Moléculaire, UMR217 CEA-CNRS, DRR, DSV, BP6 92265 Fontenay-aux-Roses Cedex, France.
Abstract:
p53 regulates the transcription of a number of genes among which are different redox-related genes. It has been proposed that these genes can induce a cellular oxidative stress leading to p53-dependent apoptosis (Polyak et al., 1997). MnSOD, the product of superoxide dismutase 2 (SOD2) gene, is one of the major cellular defences against oxidative stress. We demonstrate here 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 for the p53 function, by demonstrating that an overexpression of MnSOD decreases p53-mediated induction of apoptosis. Moreover, we demonstrate that MnSOD overexpression decreases p53-gene expression at the promoter level. These findings raise the hypothesis that p53 and SOD2 genes are mutually regulated leading to the modulation of various cellular processes including apoptosis.
Insights
The tumor suppressor p53 represses the expression of manganese superoxide dismutase (MnSOD), a key antioxidant enzyme. This mutual regulation between p53 and SOD2 influences apoptosis and cellular oxidative stress.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The p53 tumor suppressor regulates genes involved in cellular responses to stress.
- Redox-related genes are proposed to induce oxidative stress, leading to p53-dependent apoptosis.
- Manganese superoxide dismutase (MnSOD) is a critical antioxidant enzyme and the product of the SOD2 gene.
Purpose of the Study:
- To investigate the regulatory relationship between p53 and the SOD2 gene.
- To determine if p53 influences MnSOD expression and its role in apoptosis.
Main Methods:
- Reporter gene assays to assess promoter activity.
- Analysis of gene expression levels.
- Experimental manipulation of MnSOD and p53 levels.
Main Results:
- p53 represses SOD2 gene expression at the promoter level.
- Overexpression of MnSOD reduces p53-mediated apoptosis.
- MnSOD overexpression also decreases p53 gene expression at the promoter level.
Conclusions:
- p53 and SOD2 genes are mutually regulated.
- This reciprocal regulation modulates cellular processes, including apoptosis and oxidative stress response.