Related Experiment Video
Updated: Aug 11, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Airing out an antioxidant role for the tumor suppressor p53
Robert J Tomko1, Pallavi Bansal, John S Lazo
1Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Abstract:
The tumor suppressor p53 exerts its activity by preventing DNA-damaged cells from dividing until either the chromosomal repair is effected or the cell undergoes apoptosis. Reactive oxygen species (ROS) are enhanced through the action of p53-mediated transcription of apoptosis-promoting genes; however, p53 also can promote the expression of many antioxidant genes that prevent apoptosis. New research indicates that in low cellular stress, low concentrations of p53 induce the expression of antioxidant genes, whereas in severe cellular stress, high concentrations of p53 promote the expression of genes that contribute to ROS formation and p53-mediated apoptosis. p53-depleted cells injected into athymic mice increased significantly in tumor volume, whereas injected p53(+/+) cells did not grow to the same degree. Interestingly, administration of the antioxidant compound N-acetylcysteine (NAC) inhibited the growth of tumor volume in p53-depleted injected cells, and NAC supplementation of p53(-/-) mice from birth greatly decreased the number of karyotype abnormalities and tumors formed in these mice by six months of age. Thus, under normal (or low stress) conditions, p53 appears to have an antioxidant role that protects cells from oxidative DNA damage and although this effect might depend on the concentration of p53, other cellular factors likely participate in a cell's final fate.
Insights
The tumor suppressor p53 has a dual role in cell stress. Low p53 levels promote antioxidant genes, while high levels promote apoptosis. Antioxidants like NAC inhibit tumor growth in p53-deficient models.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- The tumor suppressor p53 is crucial for preventing cell division in DNA-damaged cells, initiating repair or apoptosis.
- p53's role in reactive oxygen species (ROS) production is complex, involving both pro-oxidant and antioxidant gene regulation.
- Cellular stress levels influence p53's function, with low stress favoring antioxidant responses and high stress promoting apoptosis.
Purpose of the Study:
- To investigate the concentration-dependent role of p53 in regulating antioxidant and pro-oxidant genes under varying cellular stress conditions.
- To evaluate the impact of p53 depletion on tumor growth in vivo.
- To assess the therapeutic potential of antioxidants, specifically N-acetylcysteine (NAC), in modulating p53-associated tumor development.
Main Methods:
- Analysis of p53-mediated gene expression, distinguishing between antioxidant and apoptosis-promoting genes.
- In vivo studies using p53-depleted and wild-type cells injected into athymic mice to assess tumor growth.
- Administration of N-acetylcysteine (NAC) to p53-depleted cells and p53-deficient mice to evaluate its effect on tumor volume and genomic stability.
Main Results:
- High p53 concentrations were linked to increased ROS and apoptosis, whereas low concentrations induced antioxidant gene expression.
- p53-depleted cells showed significantly increased tumor volume in mice compared to p53(+/+) cells.
- NAC administration inhibited tumor growth in p53-depleted cells and reduced karyotype abnormalities and tumor formation in p53(-/-) mice.
Conclusions:
- p53 exhibits an antioxidant role under normal or low-stress conditions, protecting against oxidative DNA damage.
- The dual role of p53 in cell fate determination is concentration-dependent and influenced by cellular stress levels.
- Antioxidant intervention, such as with NAC, may represent a viable strategy to counteract tumor development in p53-deficient contexts.
Related Concept Videos
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:36DNA Damage can Stall the Cell Cycle