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Updated: Jun 21, 2026
10:55
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Control of p53 multimerization by Ubc13 is JNK-regulated
Ivan Topisirovic1, Gustavo J Gutierrez, Meifan Chen
1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, H3T 1J4, Canada.
Summary
The p53 tumor suppressor protein
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The p53 protein is a crucial tumor suppressor regulating cell proliferation and survival.
- p53's function is controlled by transcription and protein stability.
- Ubc13, an E2 ubiquitin-conjugating enzyme, was previously shown to regulate p53 localization and activity.
Purpose of the Study:
- To investigate the regulation of p53 on translationally active polysomes.
- To elucidate the role of Ubc13 and JNK in p53 multimerization and transcriptional activation.
Main Methods:
- Demonstration of p53-Ubc13 association on polysomes.
- Analysis of p53 ubiquitination and tetramerization.
- Investigation of JNK phosphorylation at Threonine 81 on p53.
- Assessment of Ubc13-p53 complex formation and its effect on p53 multimerization.
Main Results:
- p53-Ubc13 association on polysomes requires ongoing translation and leads to p53 ubiquitination, inhibiting tetramerization.
- JNK phosphorylation of p53 at Threonine 81 on polysomes promotes Ubc13 dissociation, enabling p53 multimerization and transcriptional activation.
- Inhibition of JNK or use of a nonphosphorylatable p53 mutant sustains the Ubc13-p53 complex, blocking p53 multimerization.
Conclusions:
- A novel regulatory mechanism for p53 multimerization involving JNK and Ubc13 on polysome-bound p53 is revealed.
- This pathway fine-tunes p53's transcriptional activity through modulation of its multimerization state.
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