Ubiquitination and Degradation of Mutant p53
Open accessAbstract
While wild-type p53 is normally a rapidly degraded protein, mutant forms of p53 are stabilized and accumulate to high levels in tumor cells. In this study, we show that mutant and wild-type p53 proteins are ubiquitinated and degraded through overlapping but distinct pathways. While Mdm2 can drive the degradation of both mutant and wild-type p53, our data suggest that the ability of Mdm2 to function as a ubiquitin ligase is less important in the degradation of mutant p53, which is heavily ubiquitinated in an Mdm2-independent manner. Our initial attempts to identify ubiquitin ligases that are responsible for the ubiquitination of mutant p53 have suggested a role for the chaperone-associated ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein), although other unidentified ubiquitin ligases also appear to contribute. The contribution of Mdm2 to the degradation of mutant p53 may reflect the ability of Mdm2 to deliver the ubiquitinated mutant p53 to the proteasome.
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Increased expression of GOF mut-p53 is due to disruption of the MDM2/p53 negative feedback loop.
“Increased expression of GOF mut-p53 is due to the disruption of the MDM2/p53 negative feedback loop.”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [65]
Cites
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- Authors
- Lukashchuk, N., & Vousden, K. H.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Corresponding author
- Vousden, Karen H.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-12
- Volume
- 27
- Issue
- 23
- Pages
- 8284-8295
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2169174
- OpenAlex
- W2102368462
- Cited by
- 223
- References
- 9
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 15 · 2022: 12 · 2021: 12 · 2020: 18 · 2019: 12 · 2018: 26 · 2017: 8 · 2016: 18 · 2015: 9 · 2014: 16 · 2013: 11 · 2012: 7
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- mutant p53, p53 ubiquitination, protein degradation, MDM2, CHIP, ubiquitin ligase, proteasome, wild-type p53
- MeSH terms
- Animals, Humans, Protein Binding, Protein Processing, Post-Translational, Tumor Suppressor Protein p53, Protein Structure, Tertiary, Protein Transport, Cell Line, Tumor, Mutant Proteins, Mice, Proto-Oncogene Proteins c-mdm2, Ubiquitination
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