ArticleThe Journal of biological chemistry2012
Mutant p53 aggregates into prion-like amyloid oligomers and fibrils: implications for cancer.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.
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Who cites it
159 citing papers in PubMed, 270 citations in OpenAlex.
- The Amyloid State of Mutant p53 in Cancer.JMA journal · 2026Review
- The VHL tumor suppressor at the crossroad of protein folding, aggregation, and cancer.Molecular oncology · 2026Review
- Multi-Site Aggregation of p53: Insights from Self- and Co-Aggregation of Multiple Aggregation-Prone Regions.ACS omega · 2026Article
- Cancer-linked aggregation of p53 is driven by sequence-encoded frustration, solvation, and hydrophobic gating absent in its paralogs.Communications chemistry · 2026Article
- Magnetic graphene-based ferrite nanoparticles: synthesis, characterization, and anti-proliferative activity against some human cancer cells (RSC advances · 2026Article
- Article
- Characterization of BRCA1-Associated Protein-1 (BAP1) Aggregation Properties Induced by Cancer-Associated Mutations.Chembiochem : a European journal of chemical biology · 2025Article
- Disease-disease interactions: molecular links of neurodegenerative diseases with cancer, viral infections, and type 2 diabetes.Translational neurodegeneration · 2025Review
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- The hidden costs of imperfection: transcription errors in protein aggregation diseases.Current opinion in genetics & development · 2025Review
- Experimental kinetic mechanism of P53 condensation-amyloid aggregation.Biophysical journal · 2025Article
- Synergistic Anticancer Activity of HSP70 Inhibitor and Doxorubicin in Gain-of-Function Mutated p53 Breast Cancer Cells.Biomedicines · 2025Article
- Mesoscopic p53-rich clusters represent a new class of protein condensates.Biophysics reviews · 2025Review
- Vaccines targeting p53 mutants elicit anti-tumor immunity.Cancer letters · 2025Article
- Amyloids in bladder cancer hijack cancer-related proteins and are positive correlated to tumor stage.Scientific reports · 2025Article
- Investigating the Aggregation and Prionogenic Properties of Human Cancer-Related Proteins.Molecular and cellular biology · 2025Article
- Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.Pharmaceutics · 2024Review
- Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis.Cancer research communications · 2024Article
- Oncogenic p53 triggers amyloid aggregation of p63 and p73 liquid droplets.Communications chemistry · 2024Article
- Type I Hsp40s/DnaJs aggregates exhibit features reminiscent of amyloidogenic structures.The FEBS journal · 2024Article
99 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Over 50% of all human cancers lose p53 function. To evaluate the role of aggregation in cancer, we asked whether wild-type (WT) p53 and the hot-spot mutant R248Q could aggregate as amyloids under physiological conditions and whether the mutant could seed aggregation of the wild-type form. The central domains (p53C) of both constructs aggregated into a mixture of oligomers and fibrils. R248Q had a greater tendency to aggregate than WT p53. Full-length p53 aggregated into amyloid-like species that bound thioflavin T. The amyloid nature of the aggregates was demonstrated using x-ray diffraction, electron microscopy, FTIR, dynamic light scattering, cell viabilility assay, and anti-amyloid immunoassay. The x-ray diffraction pattern of the fibrillar aggregates was consistent with the typical conformation of cross β-sheet amyloid fibers with reflexions of 4.7 Å and 10 Å. A seed of R248Q p53C amyloid oligomers and fibrils accelerated the aggregation of WT p53C, a behavior typical of a prion. The R248Q mutant co-localized with amyloid-like species in a breast cancer sample, which further supported its prion-like effect. A tumor cell line containing mutant p53 also revealed massive aggregation of p53 in the nucleus. We conclude that aggregation of p53 into a mixture of oligomers and fibrils sequestrates the native protein into an inactive conformation that is typical of a prionoid. This prion-like behavior of oncogenic p53 mutants provides an explanation for the negative dominance effect and may serve as a potential target for cancer therapy.
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