ArticleProceedings of the National Academy of Sciences of the United States of America2009
Ultraslow oligomerization equilibria of p53 and its implications.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- A ZNF-nanobody fusion reveals SUMOylation-dependent changes in p53 protein localization.iScience · 2026Article
- 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
- TP53: the unluckiest of genes?Cell death and differentiation · 2025Review
- Correlation of p53 oligomeric status and its subcellular localization in the presence of the AML-associated NPM mutant.PloS one · 2025Article
- A molecular mechanism for the "digital" response of p53 to stress.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Influence of chain length and branching on poly(ADP-ribose)-protein interactions.Nucleic acids research · 2023Article
- Improving Reporter Gene Assay Methodology for Evaluating the Ability of Compounds to Restore P53 Activity.International journal of molecular sciences · 2022Article
- Article
- NF-κB Rel subunit exchange on a physiological timescale.Protein science : a publication of the Protein Society · 2021Article
- The complex architecture of p53 binding sites.Nucleic acids research · 2021Article
- p53 tetramerization: at the center of the dominant-negative effect of mutant p53.Genes & development · 2020Review
- Wild-type p53 oligomerizes more efficiently than p53 hot-spot mutants and overcomes mutant p53 gain-of-function via a "dominant-positive" mechanism.Oncotarget · 2018Article
- Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations.Journal of the American Society for Mass Spectrometry · 2016Article
- TP53: an oncogene in disguise.Cell death and differentiation · 2015Review
- Propagation of aggregated p53: Cross-reaction and coaggregation vs. seeding.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Escherichia coli single-stranded DNA-binding protein: nanoESI-MS studies of salt-modulated subunit exchange and DNA binding transactions.Journal of the American Society for Mass Spectrometry · 2013Article
- Mapping the structural and dynamical features of multiple p53 DNA binding domains: insights into loop 1 intrinsic dynamics.PloS one · 2013Article
- Domain-domain interactions in full-length p53 and a specific DNA complex probed by methyl NMR spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Mechanism and rates of exchange of L7/L12 between ribosomes and the effects of binding EF-G.ACS chemical biology · 2012Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor suppressor p53 is in equilibrium at cellular concentrations between dimers and tetramers. Oncogenic mutant p53 (mut) exerts a dominant-negative effect on co-expression of p53 wild-type (wt) and mut alleles in cancer cells. It is believed that wt and mut form hetero-tetramers of attenuated activity, via their tetramerization domains. Using electrospray mass spectrometry on isotopically labeled samples, we measured directly the composition and rates of formation of p53 complexes in the presence and absence of response element DNA. The dissociation of tetramers was unexpectedly very slow (t(1/2) = 40 min) at 37 degrees C, matched by slow association of dimers, which is approximately four times longer than the half-life of spontaneous denaturation of wt p53. On mixing wt tetramers with the oncogenic contact mutant R273H of low DNA affinity, we observed the same slow formation of only wt(4), wt(2)mut(2), and mut(4), in the ratio 1:2:1, on a cellular time scale. On mixing wt and mut with response element DNAs P21 and BAX, we observed only the complexes wt(4)xDNA, wt(2)mut(2)xDNA, and mut(4)xDNA, with relative dissociation constants 1:4:71 and 1:13:85, respectively, accounting for the dominant-negative effect by weakened affinity. p53 dimers assemble rapidly to tetramers on binding to response element DNA, initiated by the p53 DNA binding domains. The slow oligomerization of free p53, competing with spontaneous denaturation, has implications for the possible regulation of p53 by binding proteins and DNA that affect tetramerization kinetics as well as equilibria.
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