Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Death Differ. 2013 Jan;20(1):117-29. doi: 10.1038/cdd.2012.102. Epub 2012 Aug 24.

The critical role of catalase in prooxidant and antioxidant function of p53.

Author information

1
DNA Damage Response Network Center, Chosun University School of Medicine, Gwangju, South Korea.

Abstract

The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2-catalase and p53/PIG3-catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively.

PMID:
22918438
PMCID:
PMC3524643
DOI:
10.1038/cdd.2012.102
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center