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Updated: Jun 8, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Regulation of apoptosis by p53-inducible transmembrane protein containing sushi domain
Hongyan Cui1, Hiroki Kamino, Yasuyuki Nakamura
1Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Abstract:
The tumor suppressor p53 is a transcription factor that induces the transcription of various target genes in response to DNA damage and it protects the cells from malignant transformation. In this study, we performed cDNA microarray analysis and found that the transmembrane protein containing sushi domain (TMPS) gene, which encodes a putative type I transmembrane protein, is a novel p53-target gene. TMPS contains a sushi domain in the extracellular region, which is associated with protein-protein interaction. TMPS expression is induced by endogenous p53 under genotoxic stress in several cancer cell lines. Reporter assay revealed p53-dependent transactivation of the p53 binding-sites (BSs) located in the intron 1 of TMPS. Chromatin immunoprecipitation (ChIP) assay showed that p53 binds to these BSs in vivo. Overexpression of TMPS induced apoptosis through the activation of caspase-3, 8, and 9 in various cancer cell lines. Moreover, γ-irradiation induced the expression of TMPS mRNA in the spleen and colon of p53+/+ mice but not in those of p53-/- mice. These data indicate that TMPS may play a role in p53-dependent apoptosis under DNA damage condition.
Insights
The tumor suppressor p53 activates the TMPS gene, a novel target. TMPS promotes apoptosis in cancer cells, highlighting its role in DNA damage response.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The p53 tumor suppressor is crucial for cellular response to DNA damage, preventing malignant transformation.
- Identifying novel p53 target genes is essential for understanding its tumor-suppressive functions.
Purpose of the Study:
- To identify and characterize novel p53 target genes involved in DNA damage response.
- To investigate the role of the transmembrane protein containing sushi domain (TMPS) gene as a p53 target.
Main Methods:
- cDNA microarray analysis to identify potential p53 targets.
- Reporter assays and chromatin immunoprecipitation (ChIP) to confirm p53 binding and transactivation.
- Apoptosis assays (caspase activation) and mouse models (p53+/+ vs. p53-/-) to assess TMPS function.
Main Results:
- TMPS was identified as a novel p53 target gene.
- p53 directly binds to and transactivates the TMPS gene in response to genotoxic stress.
- TMPS overexpression induces apoptosis via caspase activation in cancer cell lines.
- TMPS expression is induced by DNA damage in a p53-dependent manner in mouse tissues.
Conclusions:
- TMPS is a novel p53 target gene regulated by p53 under genotoxic stress.
- TMPS plays a role in p53-dependent apoptosis, contributing to tumor suppression.
- TMPS represents a potential therapeutic target in cancer treatment.
Related Concept Videos
The Intrinsic Apoptotic Pathway
Regulation of the Unfolded Protein Response
Abnormal Proliferation
The Extrinsic Apoptotic Pathway
Negative Regulator Molecules
Caspases

