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Updated: May 18, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 counteracts reprogramming by inhibiting mesenchymal-to-epithelial transition
R Brosh1, Y Assia-Alroy, A Molchadsky
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. ranbroshran@gmail.com
Cell Death and Differentiation
|September 22, 2012
Summary
Inhibiting the p53-p21 pathway enhances somatic cell reprogramming by promoting mesenchymal-to-epithelial transition (MET). This discovery offers new strategies for improving therapeutic cell generation and understanding cell plasticity.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Somatic cell reprogramming holds therapeutic promise but is inefficient.
- Inhibiting the p53 tumor suppressor facilitates reprogramming by limiting proliferation and apoptosis.
- Mesenchymal-to-epithelial transition (MET) is crucial for fibroblast reprogramming.
Purpose of the Study:
- To investigate if p53 impedes reprogramming by affecting MET.
- To elucidate the mechanism by which p53 influences MET during reprogramming.
Main Methods:
- Investigated the role of p53 in MET during early reprogramming phases.
- Utilized transcriptome analysis to identify gene expression changes.
- Assessed the correlation between p53 activity and epithelial marker expression.
- Determined the involvement of p21 in p53's inhibitory effect on MET.
Main Results:
- p53 restricts MET during early reprogramming, primarily by inhibiting Klf4-mediated epithelial gene activation.
- Transcriptome analysis revealed Klf4 induces an epithelial gene signature in p53-deficient cells.
- E-Cadherin expression negatively correlates with p53 activity in mesenchymal cells.
- The p53-p21 axis mediates the inhibition of MET.
Conclusions:
- Inhibiting the p53-p21 axis promotes MET, making mesenchymal cells more receptive to reprogramming.
- This study reveals a novel mechanism of p53-mediated reprogramming restraint.
- Highlights p53's role in regulating cellular plasticity and reprogramming efficiency.
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