Drane P, Bravard A, Bouvard V, May E
Commissariat à l'Energie Atomique (CEA), Laboratoire de Cancérogenèse Moléculaire, UMR217 CEA-CNRS, DRR, DSV, BP6 92265 Fontenay-aux-Roses Cedex, France.
Oncogene. 2001 Jan 25;20(4):430-9. doi: 10.1038/sj.onc.1204101.
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.
p53调控许多基因的转录，其中包括不同的氧化还原相关基因。有人提出，这些基因可诱导细胞氧化应激，导致p53依赖的细胞凋亡（Polyak等人，1997年）。锰超氧化物歧化酶（MnSOD）是超氧化物歧化酶2（SOD2）基因的产物，是细胞对抗氧化应激的主要防御机制之一。我们在此证明p53能够抑制SOD2基因的表达，且这种抑制发生在启动子水平。通过证明MnSOD的过表达会降低p53介导的细胞凋亡诱导作用，我们展示了这种调控对p53功能的重要性。此外，我们证明MnSOD的过表达在启动子水平降低了p53基因的表达。这些发现提出了一个假设，即p53和SOD2基因相互调控，从而导致包括细胞凋亡在内的各种细胞过程的调节。
