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Updated: Aug 19, 2026
Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
p53-dependent induction of serine proteases in irradiated mouse colon
Shih-Wen Lin1, Michelle Cook, Niklas Finnberg
1University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Abstract:
Tumor suppressor p53 induces apoptosis through the transactivation of target genes. Previous work has shown that p53-dependent gene expression changes in response to ionizing radiation are tissue specific. To determine critical p53 target genes in the colon, we irradiated wild-type and p53-null mice and examined the global p53 gene expression patterns in response to ionizing radiation. Microarray analysis using the Affymetrix MOE430A genechip showed that many of the genes that increased in a p53-dependent manner are serine proteases (e.g., elastase, trypsin) and other proteases (e.g., carboxypeptidases). Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blots were used to validate microarray results on trypsin 4, carboxypeptidase A1, and elastase-2, three genes that have potential p53-binding elements. Further study of tissue specific mediators of p53-dependent responses such as serine proteases will greatly increase understanding of in vivo p53-dependent pathways within the colon triggered by ionizing radiation.
Insights
Tumor suppressor p53
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The tumor suppressor p53 protein is crucial for inducing apoptosis.
- p53-dependent gene expression is known to be tissue-specific following ionizing radiation.
- Understanding p53's role in the colon is essential for cancer research.
Purpose of the Study:
- To identify critical p53 target genes in the colon.
- To investigate global p53 gene expression patterns after ionizing radiation exposure in mice.
Main Methods:
- Irradiation of wild-type and p53-null mice.
- Microarray analysis (Affymetrix MOE430A genechip) to assess gene expression.
- Validation of key genes using RT-PCR, immunohistochemistry, and Western blots.
Main Results:
- Ionizing radiation induced p53-dependent expression of several serine proteases and other proteases in the colon.
- Trypsin 4, carboxypeptidase A1, and elastase-2 were identified as potential p53 target genes.
- These genes showed p53-binding elements, confirming their regulatory relationship.
Conclusions:
- Serine proteases and other proteases are key mediators of p53-dependent responses in the colon.
- This study enhances the understanding of in vivo p53 pathways activated by ionizing radiation in the colon.
