The antioxidant function of the p53 tumor suppressor

We show that in addition p53 protects the genome from oxidation by reactive oxygen species, a major cause for DNA damage and genetic instability

Anna A Sablina; Andrei V Budanov; Galina V Ilyinskaya; Larissa S Agapova; Julia E Kravchenko; Peter M Chumakov

2005

Scholarcy highlights

  • The major function for the p53 tumor suppressor is to restrict abnormal or stress-exposed cells before damage to DNA is converted to inherited mutation1
  • We show that in addition p53 down-regulates intracellular reactive oxygen species levels reducing probability of genetic alterations
  • The antioxidant function for p53 was not expected as p53 was known as potent pro-oxidant inducing a set of ROS-generating genes, which contribute to apoptosis8
  • We show that the pro-oxidant function of p53 is tightly linked to release of mitochondrial ROS during stress-induced apoptosis
  • The anti-oxidant function of p53 is mediated through a set of antioxidant genes, which are responsive to lower levels of p53 in non-stressed or physiologically-stressed cells
  • We propose that the antioxidant function of p53 represents an important component of its suppressor activity, which decreases probability of genetic alterations and assists the survival and repair of cells with minor injuries
  • Our results on selective inhibition of p53-deficient xenograft growth by NAC supplementation suggest that the introduction of antioxidants to cancer therapy schemes could improve genetic stability of p53deficient tumor cells and retard cancer progression

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