ArticleChemical science2021
Single-molecule analysis of interaction between p53TAD and MDM2 using aerolysin nanopores.
Article in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- Single-Molecule Techniques for Probing the Conformation, Dynamics and Interactions of Intrinsically Disordered Proteins.Biophysics reviews · 2025Article
- Identification of RBM15 as a prognostic biomarker in prostate cancer involving the regulation of prognostic m6A-related lncRNAs.European journal of medical research · 2024Article
- Visualizing single-molecule conformational transition and binding dynamics of intrinsically disordered proteins.Nature communications · 2023Article
- Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore.Nature communications · 2023Article
- Determination of protein conformation and orientation at buried solid/liquid interfaces.Chemical science · 2023Article
- Design of a Current Sensing System with TIA Gain of 160 dBΩ and Input-Referred Noise of 1.8 pASensors (Basel, Switzerland) · 2023Article
- Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials.Journal of hematology & oncology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions (PPIs) are regarded as important, but undruggable targets. Intrinsically disordered p53 transactivation domain (p53TAD) mediates PPI with mouse double minute 2 (MDM2), which is an attractive anticancer target for therapeutic intervention. Here, using aerolysin nanopores, we probed the p53TAD peptide/MDM2 interaction and its modulation by small-molecule PPI inhibitors or p53TAD phosphorylation. Although the p53TAD peptide showed short-lived (<100 ms) translocation, the protein complex induced the characteristic extraordinarily long-lived (0.1 s ∼ tens of min) current blockage, indicating that the MDM2 recruitment by p53TAD peptide almost fully occludes the pore. Simultaneously, the protein complex formation substantially reduced the event frequency of short-lived peptide translocation. Notably, the addition of small-molecule PPI inhibitors, Nutlin-3 and AMG232, or Thr18 phosphorylation of p53TAD peptide, were able to diminish the extraordinarily long-lived events and restore the short-lived translocation of the peptide rescued from the complex. Taken together, our results elucidate a novel mechanism of single-molecule sensing for analyzing PPIs and their inhibitors using aerolysin nanopores. This novel methodology may contribute to remarkable improvements in drug discovery targeted against undruggable PPIs.
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Registered trials
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.