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p53 isoforms can regulate p53 transcriptional activity
Open accessAbstract
The recently discovered p53-related genes, p73 and p63, express multiple splice variants and N-terminally truncated forms initiated from an alternative promoter in intron 3. To date, no alternative promoter and multiple splice variants have been described for the p53 gene. In this study, we show that p53 has a gene structure similar to the p73 and p63 genes. The human p53 gene contains an alternative promoter and transcribes multiple splice variants. We show that p53 variants are expressed in normal human tissue in a tissue-dependent manner. We determine that the alternative promoter is conserved through evolution from Drosophila to man, suggesting that the p53 family gene structure plays an essential role in the multiple activities of the p53 family members. Consistent with this hypothesis, p53 variants are differentially expressed in human breast tumors compared with normal breast tissue. We establish that p53β can bind differentially to promoters and can enhance p53 target gene expression in a promoter-dependent manner, while Δ133p53 is dominant-negative toward full-length p53, inhibiting p53-mediated apoptosis. The differential expression of the p53 isoforms in human tumors may explain the difficulties in linking p53 status to the biological properties and drug sensitivity of human cancer.
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“Among them are p53β, a C-terminally truncated isoform that cooperates with p53FL, and Δ133p53, an N-terminally truncated isoform that inhibits p53FL in a dominant-negative manner (14).”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [14]
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“these data suggest a mechanism by which Δ133p53, which lacks the transactivation domain (14), transcriptionally activates CD28 mRNA expression.”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [14]
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Metadata
- Authors
- Bourdon, J.-C., Fernandes, K., Murray-Zmijewski, F., Liu, G., Diot, A., Xirodimas, D. P., Saville, M. K., & Lane, D. P.
- Affiliations
- University of Dundee (GB)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-08-30
- Volume
- 19
- Issue
- 18
- Pages
- 2122-2137
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1221884
- OpenAlex
- W2155570392
- Cited by
- 810
- References
- 43
- Citations by year
- 2026: 19 · 2025: 30 · 2024: 26 · 2023: 30 · 2022: 25 · 2021: 37 · 2020: 29 · 2019: 28 · 2018: 41 · 2017: 27 · 2016: 40 · 2015: 27 · 2014: 49 · 2013: 38 · 2012: 48
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- HAL (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Genes
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- p53 isoforms, alternative promoters, p73, p63, Δ133p53, dominant-negative p53, p53 transcriptional activity, breast tumors, Drosophila, apoptosis, cancer drug sensitivity
- MeSH terms
- Animals, Breast Neoplasms, Drosophila, Humans, Introns, Luciferases, Promoter Regions, Genetic, RNA, Messenger, Transcription, Genetic, Genetic Variation, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Apoptosis, Genes, Insect, Alternative Splicing, Genes, Reporter, HT29 Cells, Evolution, Molecular, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor
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