ArticleThe EMBO journal2000
Mechanism of rescue of common p53 cancer mutations by second-site suppressor mutations.
Article in The EMBO journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Determinants of CBiomolecules · 2026Article
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53.Frontiers in pharmacology · 2025Review
- Navigating the complexity of p53-DNA binding: implications for cancer therapy.Biophysical reviews · 2024Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- P53 together with ferroptosis: a promising strategy leaving cancer cells without escape.Acta biochimica et biophysica Sinica · 2024Article
- Cellular and epigenetic perspective of protein stability and its implications in the biological system.Epigenomics · 2024Review
- Multidimensional quantitative phenotypic and molecular analysis reveals neomorphic behaviors of p53 missense mutants.NPJ breast cancer · 2023Article
- Small-molecule correctors and stabilizers to target p53.Trends in pharmacological sciences · 2023Review
- Review
- p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations.Diagnostic pathology · 2022Article
- Mechanistic insights into global suppressors of protein folding defects.PLoS genetics · 2022Article
- The effect of electron dose on positive polymethyl methacrylate resist for nanolithography of gold bowtie nanoantennas.Heliyon · 2022Article
- Identification of stabilizing point mutations through mutagenesis of destabilized protein libraries.The Journal of biological chemistry · 2022Article
- SWAAT Bioinformatics Workflow for Protein Structure-Based Annotation of ADME Gene Variants.Journal of personalized medicine · 2022Article
- Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis.Cancers · 2022Review
- Caffeic acid phenethyl ester (CAPE) confers wild type p53 function in p53Discover oncology · 2021Article
- Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members.International journal of molecular sciences · 2021Review
- Targeting mutant p53 for cancer therapy: direct and indirect strategies.Journal of hematology & oncology · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
The core domain of p53 is extremely susceptible to mutations that lead to loss of function. We analysed the stability and DNA-binding activity of such mutants to understand the mechanism of second-site suppressor mutations. Double-mutant cycles show that N239Y and N268D act as 'global stability' suppressors by increasing the stability of the cancer mutants G245S and V143A-the free energy changes are additive. Conversely, the suppressor H168R is specific for the R249S mutation: despite destabilizing wild type, H168R has virtually no effect on the stability of R249S, but restores its binding affinity for the gadd45 promoter. NMR structural comparisons of R249S/H168R and R249S/T123A/H168R with wild type and R249S show that H168R reverts some of the structural changes induced by R249S. These results have implications for possible drug therapy to restore the function of tumorigenic mutants of p53: the function of mutants such as V143A and G245S is theoretically possible to restore by small molecules that simply bind to and hence stabilize the native structure, whereas R249S requires alteration of its mutant native structure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.