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Updated: Aug 21, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Upregulation of ITM2A by p53 activation modulates p53 function through physical interaction
Sim Namkoong1,2, Minsu Jang1, Jeong In Lee2
1Division of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
Abstract:
The tumor suppressor p53 plays a crucial role in preventing cancer development, and its dysfunction is frequently observed in various cancers. This study identifies a novel regulatory interaction between p53 and ITM2A. We found that p53 upregulates ITM2A expression, while ITM2A in turn inhibits p53 function, suggesting a negative feedback loop. ITM2A mRNA levels were reduced across multiple tumor types, particularly in those harboring mutant p53, and low ITM2A expression correlated with poor patient survival. Mechanistically, ITM2A physically interacts with p53, selectively modulates its phosphorylation (reducing Ser392 while enhancing Ser37), and promotes cytoplasmic accumulation of p53. These modifications collectively suppress p53-dependent transcription, an effect consistently observed across multiple cell lines under both basal conditions and upon physiological p53 activation by genotoxic stress. Conversely, ITM2A depletion enhances p53 nuclear accumulation and transcriptional activity. These findings reveal a novel autoregulatory circuit wherein p53 induces ITM2A expression, which then attenuates p53 activity, suggesting ITM2A as a potential prognostic marker and therapeutic target for cancers with dysregulated p53 signaling.
Insights
The tumor suppressor p53 regulates ITM2A, which then inhibits p53 activity, forming a feedback loop. Reduced ITM2A levels correlate with poor survival in cancers with faulty p53.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- The tumor suppressor p53 is critical for preventing cancer.
- p53 dysfunction is common in many cancers.
- A novel interaction between p53 and ITM2A was investigated.
Purpose of the Study:
- To identify and characterize the regulatory relationship between p53 and ITM2A.
- To explore the functional consequences of this interaction in cancer.
Main Methods:
- Western blotting and quantitative PCR to assess protein and mRNA levels.
- Immunoprecipitation to confirm physical interaction.
- Phosphorylation site analysis and subcellular localization studies.
- Reporter assays to measure transcriptional activity.
Main Results:
- p53 upregulates ITM2A expression, creating a negative feedback loop.
- ITM2A expression is reduced in multiple tumor types, especially with mutant p53.
- Low ITM2A correlates with decreased patient survival.
- ITM2A modulates p53 phosphorylation, promotes cytoplasmic localization, and suppresses p53 transcriptional activity.
- ITM2A depletion enhances p53 nuclear accumulation and activity.
Conclusions:
- A novel p53-ITM2A autoregulatory circuit was discovered.
- ITM2A acts as a negative regulator of p53.
- ITM2A may serve as a prognostic marker and therapeutic target in cancers with p53 alterations.
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