ArticlePhysical chemistry chemical physics : PCCP2016
Self-aggregation and coaggregation of the p53 core fragment with its aggregation gatekeeper variant.
Article in Physical chemistry chemical physics : PCCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Multi-Site Aggregation of p53: Insights from Self- and Co-Aggregation of Multiple Aggregation-Prone Regions.ACS omega · 2026Article
- Insights into Network of Hot Spots of Aggregation in Nucleophosmin 1.International journal of molecular sciences · 2022Article
- Insights into Allosteric Mechanisms of the Lung-Enriched p53 Mutants V157F and R158L.International journal of molecular sciences · 2022Article
- Deciphering the mechanisms of HPV E6 mutations in the destabilization of E6/E6AP/p53 complex.Biophysical journal · 2022Article
- Unraveling the Influence of K280 Acetylation on the Conformational Features of Tau Core Fragment: A Molecular Dynamics Simulation Study.Frontiers in molecular biosciences · 2021Article
- Therapeutic potential of ReACp53 targeting mutant p53 protein in CRPC.Prostate cancer and prostatic diseases · 2020Article
- p53 Isoforms and Their Implications in Cancer.Cancers · 2018Review
- Molecular Recognition between Aβ-Specific Single-Domain Antibody and Aβ Misfolded Aggregates.Antibodies (Basel, Switzerland) · 2018Article
- Investigating the Influence of Magnesium Ions on p53-DNA Binding Using Atomic Force Microscopy.International journal of molecular sciences · 2017Article
- Assemblies of amyloid-β30-36 hexamer and its G33V/L34T mutants by replica-exchange molecular dynamics simulation.PloS one · 2017Article
- Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Recent studies suggested that p53 aggregation can lead to loss-of-function (LoF), dominant-negative (DN) and gain-of-function (GoF) effects, with adverse cancer consequences. The p53 aggregation-nucleating (251)ILTIITL(257) fragment is a key segment in wild-type p53 aggregation; however, an I254R mutation can prevent it. It was suggested that self-assembly of wild-type p53 and its cross-interaction with mutants differ from the classical amyloid nucleation-growth mechanism. Here, using replica exchange molecular dynamics (REMD) simulations, we studied the cross-interactions of this p53 core fragment and its aggregation rescue I254R mutant. We found that the core fragment displays strong aggregation propensity, whereas the gatekeeper I254R mutant tends to be disordered, consistent with experiments. Our cross-interaction results reveal that the wild-type p53 fragment promotes β-sheet formation of the I254R mutant by shifting the disordered mutant peptides into aggregating states. As a result, the system has similar oligomeric structures, inter-peptide interactions and free energy landscape as the wild type fragment does, revealing a prion-like process. We also found that in the cross-interaction system, the wild-type species has higher tendency to interact with the mutant than with itself. This phenomenon illustrates synergistic effects between the p53 (251)ILTIITL(257) fragment and the mutant resembling prion cross-species propagation, cautioning against exploiting it in drug discovery.
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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.