P53: Stability from the Ubiquitin–Proteasome System and Specific 26S Proteasome Inhibitors
Open accessAbstract
Protein p53 is degraded by the 26S proteasome, a protein complex that breaks down cellular proteins. Degradation begins with activation of the protein ubiquitin (Ub) by the ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes, and ubiquitin E3 ligases, linking Ub or the polyubiquitin chain to p53 and marking it for degradation by the 26S proteasome. E3 ubiquitin ligases participate in this process and regulate p53 stability. There are compounds that inhibit the 26S proteasome and interfere at the p53 level, and some of these inhibitors are used to treat cancer and other diseases and can stabilize tumor suppressor proteins through the p53 pathway. This review discusses how the ubiquitin-proteasome system, p53, and these compounds are related.
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MDM2 can cooperate with MDMX to kinetically enhance p53 polyubiquitination, resulting in p53 stability and tumor occurrence.
“MDM2 can cooperate with MDMX (mouse double minute X) to kinetically enhance p53 polyubiquitination, resulting in p53 stability and the occurrence of tumors [11–13].”
From Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials (2022) · cites this paper as [13]
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- Authors
- do Patrocinio, A. B., Rodrigues, V., & Guidi Magalhães, L.
- Affiliations
- Research Group on Natural Products (Center for Research in Sciences and Technology), Universidade de Franca, Av. Dr. Armando de Sales Oliveira, 201 - Parque Universitário, Franca, São Paulo 14404-600, Brazil
- Universidade de São Paulo (BR)
- Venue
- ACS Omega
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-01-27
- Volume
- 7
- Issue
- 5
- Pages
- 3836-3843
- ISSN
- 2470-1343 (ISSN-L)
- PMC
- PMC8829948
- OpenAlex
- W4210342072
- Cited by
- 36
- References
- 24
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 2
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ACS Omega (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Funda????o de Amparo ?? Pesquisa do Estado de S??o Paulo (2016/06769-2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- p53, ubiquitin-proteasome system, 26S proteasome, proteasome inhibitors, protein degradation, E3 ubiquitin ligase, ubiquitination, tumor suppressor proteins, cancer therapy
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