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Updated: May 19, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
The critical role of catalase in prooxidant and antioxidant function of p53
1DNA 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.
Insights
The tumor suppressor p53 regulates reactive oxygen species (ROS) by interacting with catalase. p53 uses p53R2 for antioxidant effects and PIG3 to promote oxidative stress during DNA damage.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- The tumor suppressor p53 is a key regulator of cellular processes, including the management of intracellular reactive oxygen species (ROS).
- Downstream molecular mechanisms by which p53 controls ROS levels are not fully understood.
Purpose of the Study:
- To elucidate the downstream mediators involved in p53-dependent regulation of intracellular ROS.
- To investigate the interaction between p53, its targets, and catalase in controlling ROS homeostasis.
Main Methods:
- Investigated physical and functional interactions between p53, p53R2, PIG3, and catalase.
- Assessed the impact of these interactions on catalase activity and ROS levels under varying stress conditions.
Main Results:
- p53, p53R2, and PIG3 interact with catalase to regulate intracellular ROS, with the mechanism dependent on stress intensity.
- Under physiological conditions, p53R2 enhances catalase activity, protecting against endogenous ROS.
- Following genotoxic stress, p53 and PIG3 inhibit catalase activity, promoting an oxidative state that may enhance apoptosis.
Conclusions:
- Catalase plays a crucial role in p53-mediated ROS regulation.
- The p53/p53R2-catalase pathway is vital for ROS control under physiological conditions.
- The p53/PIG3-catalase pathway is critical for ROS regulation during the DNA damage response.
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