ArticleBiophysical journal2020
Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Mutant p53Molecular oncology · 2026Article
- A p53Molecular therapy. Oncology · 2026Article
- TP53 mutation heterogeneity reveals distinct prognoses in mantle cell lymphoma.Annals of hematology · 2026Article
- GD3 synthase drives resistance to p53-induced apoptosis in breast cancer by modulating mitochondrial function.Oncogene · 2025Article
- TP53-Mutated Acute Myeloid Leukemia and Blast Phase Myeloproliferative Neoplasm: Distinct Mutation Leads to Poorer Prognosis.European journal of haematology · 2025Article
- Sensitizing Immune-Refractory Ovarian Tumors via p53 Mutation-Tailored Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Article
- Review
- Doxorubicin catalyses self-assembly of p53 by phase separation.Current research in structural biology · 2024Article
- Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms.PloS one · 2024Article
- Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions.Communications biology · 2023Article
- Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry.Life (Basel, Switzerland) · 2022Article
- Characterization of full-length p53 aggregates and their kinetics of formation.Biophysical journal · 2022Article
- Potential of rescue and reactivation of tumor suppressor p53 for cancer therapy.Biophysical reviews · 2022Review
- Comprehensive Analysis of the Carcinogenic Process, Tumor Microenvironment, and Drug Response in HPV-Positive Cancers.Frontiers in oncology · 2022Article
- Relevance of Amorphous and Amyloid-Like Aggregates of the p53 Core Domain to Loss of its DNA-Binding Activity.Frontiers in molecular biosciences · 2022Article
- Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function.Nature communications · 2021Article
- An integrated view of p53 dynamics, function, and reactivation.Current opinion in structural biology · 2021Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in p53 protein, especially in the DNA-binding domain, is one of the major hallmarks of cancer. The R273 position is a DNA-contact position and has several oncogenic variants. Surprisingly, cancer patients carrying different mutant variants of R273 in p53 have different survival rates, indicating that the DNA-contact inhibition may not be the sole reason for reduced survival with R273 variants. Here, we probed the properties of three major oncogenic variants of the wild-type (WT) p53: [R273H]p53, [R273C]p53, and [R273L]p53. Using a series of biophysical, biochemical, and theoretical simulation studies, we observe that these oncogenic variants of the p53 not only suffer a loss in DNA binding, but they also show distinct structural stability, aggregation, and toxicity profiles. The WTp53 and the [R273H]p53 show the least destabilization and aggregation propensity. [R273C]p53 aggregation is disulfide mediated, leading to cross-β, thioflavin-T-positive aggregates, whereas hydrophobic interactions dominate self-assembly in [R273L]p53, leading to a mixture of amyloid and amorphous aggregates. Molecular dynamics simulations indicate different contact maps and secondary structures for the different variants along the course of the simulations. Our study indicates that each of the R273 variants has its own distinct property of stability and self-assembly, the molecular basis of which may lead to different types of cancer pathogenesis in vivo. These studies will aid the design of therapeutic strategies for cancer using residue-specific or process-specific protein aggregation as a target.
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