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Updated: Jun 18, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Targeting the ubiquitin-proteasome system to activate wild-type p53 for cancer therapy
Nerea Allende-Vega1, Mark K Saville
1CR-UK Cell Transformation Research Group, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
Abstract:
Ubiquitination plays a key role in regulating the tumour suppressor p53. It targets p53 for degradation by the 26S proteasome. The ubiquitin pathway also regulates the activity and localisation of p53. Ubiquitination requires ubiquitin-activating and -conjugating enzymes and ubiquitin ligases. In addition, ubiquitination can be reversed by the action of deubiquitinating enzymes. Here we give an overview of the role of components of the ubiquitin-proteasome system in the regulation of p53 and review progress in targeting these proteins to activate wild-type p53 for the treatment of cancer.
Insights
The ubiquitin-proteasome system regulates the tumor suppressor p53, targeting it for degradation. Targeting this system offers a strategy to activate p53 for cancer therapy.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- The tumor suppressor p53 is a critical regulator of cellular processes.
- Ubiquitination is a key post-translational modification that controls protein stability and function.
- The ubiquitin-proteasome system (UPS) is essential for targeted protein degradation.
Purpose of the Study:
- To provide an overview of how the ubiquitin-proteasome system regulates p53.
- To review strategies for targeting UPS components to activate wild-type p53.
- To explore the therapeutic potential of activating p53 in cancer treatment.
Main Methods:
- Literature review of the ubiquitin-proteasome system's role in p53 regulation.
- Analysis of enzymes involved in ubiquitination and deubiquitination.
- Examination of therapeutic approaches targeting UPS components.
Main Results:
- Ubiquitination targets p53 for degradation by the 26S proteasome.
- The ubiquitin pathway influences p53 activity and cellular localization.
- Deubiquitinating enzymes can reverse p53 ubiquitination.
- Targeting UPS components shows promise for activating wild-type p53.
Conclusions:
- The ubiquitin-proteasome system is a crucial regulator of p53.
- Modulating the UPS offers a viable therapeutic strategy for cancer treatment by activating p53.
- Further research into targeting UPS components could lead to novel cancer therapies.
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