The Isoforms of the p53 Protein
Open accessAbstract
p53 is a transcription factor with a key role in the maintenance of genetic stability and therefore preventing cancer formation. It belongs to a family of genes composed of p53, p63, and p73. The p63 and p73 genes have a dual gene structure with an internal promoter in intron-3 and together with alternative splicing, can express 6 and 29 mRNA variants, respectively. Such a complex expression pattern had not been previously described for the p53 gene, which was not consistent with our understanding of the evolution of the p53 gene family. Consequently, we revisited the human p53 gene structure and established that it encodes nine different p53 protein isoforms because of alternative splicing, alternative promoter usage, and alternative initiation sites of translation. Therefore, the human p53 gene family (p53, p63, and p73) has a dual gene structure. We determined that the dual gene structure is conserved in Drosophila and in zebrafish p53 genes. The conservation through evolution of the dual gene structure suggests that the p53 isoforms play an important role in p53 tumor-suppressor activity. We and others have established that the p53 isoforms can regulate cell-fate outcome in response to stress, by modulating p53 transcriptional activity in a promoter and stress-dependent manner. We have also shown that the p53 isoforms are abnormally expressed in several types of human cancers, suggesting that they play an important role in cancer formation. The determination of p53 isoforms' expression may help to link clinical outcome to p53 status and to improve cancer patient treatment.
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Human TP53 produces at least 13 natural isoforms through alternative splicing and alternative promoter use.
“The human TP53 gene encodes, in addition to full-length p53 protein (p53FL), at least 13 natural isoforms due to alternative splicing and usage of alternative promoters (13).”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [13]
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- Authors
- Khoury, M. P., & Bourdon, J.-C.
- Affiliations
- Inserm (FR)
- ORCID
- Bourdon, J.-C.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-11-25
- Volume
- 2
- Issue
- 3
- Pages
- a000927-a000927
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC2829963
- OpenAlex
- W2158746638
- Cited by
- 191
- References
- 37
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 7 · 2022: 14 · 2021: 10 · 2020: 7 · 2019: 17 · 2018: 18 · 2017: 10 · 2016: 11 · 2015: 7 · 2014: 19 · 2013: 16 · 2012: 19
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Cancer Research UK
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53 isoforms, p63, p73, alternative splicing, alternative promoters, alternative translation initiation, tumor suppressor activity, genetic stability, cancer, stress response, cell fate regulation
- MeSH terms
- Animals, Humans, Models, Biological, Models, Genetic, Neoplasms, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Alternative Splicing, Cell Lineage, Protein Isoforms
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