ArticleMolecular and cellular biology2004
How many mutant p53 molecules are needed to inactivate a tetramer?
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 153 citations in OpenAlex.
- Trial
- Unbiased assessment of APR-246 responsive p53 mutants in ovarian cancer.Cell death discovery · 2026Article
- Review
- Lung cancer-enriched p53 mutants occupy canonical p53 target genes without activating transcription, revealing a distinct loss-of-function behavior.bioRxiv : the preprint server for biology · 2026Article
- Biology of p53 protein isoforms and their significance in hematological malignancies.Frontiers in oncology · 2026Review
- Article
- The Prolonged Half-Life of the p53 Missense Variant R248Q Promotes Accumulation and Heterotetramer Formation with Wild-Type p53 to Exert the Dominant-Negative Effect.Cancer research · 2025Article
- Heterozygous TP63 pathogenic variants in isolated primary ovarian insufficiency.Journal of assisted reproduction and genetics · 2023Article
- The Competition of Yin and Yang: Exploring the Role of Wild-Type and Mutant p53 in Tumor Progression.Biomedicines · 2023Article
- Distinct interactors define the p63 transcriptional signature in epithelial development or cancer.The Biochemical journal · 2022Article
- P63 and P73 Activation in Cancers with p53 Mutation.Biomedicines · 2022Review
- Mutant p53: it's not all one and the same.Cell death and differentiation · 2022Review
- Should mutant TP53 be targeted for cancer therapy?Cell death and differentiation · 2022Review
- NAMPT Inhibitor and P73 Activator Represses P53 R175H Mutated HNSCC Cell Proliferation in a Synergistic Manner.Biomolecules · 2022Article
- Mutations in TP53 and PIK3CA genes in hepatocellular carcinoma patients are associated with chronic Schistosomiasis.Saudi journal of biological sciences · 2022Article
- Review
- A general approach to protein folding using thermostable exoshells.Nature communications · 2021Article
- Review
- p53 tetramerization: at the center of the dominant-negative effect of mutant p53.Genes & development · 2020Review
- Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor p53 is transcription factor composed of four identical subunits. The majority of the mutations in p53 are missense mutations that impair DNA binding. On the other hand, the p53-related p63 and p73 genes are rarely mutated, but many cell types express natural variants lacking the N-terminal transactivation domain (NDelta). Compelling evidence indicates that both the DNA binding-defective and NDelta mutants can impair the function of wild-type p53 in a dominant-negative manner. Interestingly, it is uncertain how many mutant subunit(s) a p53 tetramer can tolerate. In this study, we first made theoretical predictions based on the number of mutant p53 monomers needed to inactivate a tetramer and then tested how well the experimental data fit the predicted values. Surprisingly, these experiments reveal that DNA binding-defective p53 mutants (R249S and R273H) are very ineffective in impairing the transcriptional activity of p53: at least three mutants are required to inactivate a tetramer. In marked contrast, p53NDelta is a very potent inhibitor of p53: one NDelta subunit per tetramer is sufficient to abolish the transcriptional activity. DNA binding is not necessary for the NDelta proteins to inactivate p53. Similarly, NDelta variants of p63 and p73 are also powerful inhibitors of members of the p53 family. These results have important implications for our thinking about the mechanism of tumorigenesis involving missense p53 mutants or the N-terminally truncated isoforms.
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