ArticleProceedings of the National Academy of Sciences of the United States of America2015
Propagation of aggregated p53: Cross-reaction and coaggregation vs. seeding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Disease-disease interactions: molecular links of neurodegenerative diseases with cancer, viral infections, and type 2 diabetes.Translational neurodegeneration · 2025Review
- Article
- Experimental kinetic mechanism of P53 condensation-amyloid aggregation.Biophysical journal · 2025Article
- Mesoscopic p53-rich clusters represent a new class of protein condensates.Biophysics reviews · 2025Review
- Oncogenic p53 triggers amyloid aggregation of p63 and p73 liquid droplets.Communications chemistry · 2024Article
- Impacts of cytoplasmic p53 aggregates on the prognosis and the transcriptome in lung squamous cell carcinoma.Cancer science · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- p53 amyloid pathology is correlated with higher cancer grade irrespective of the mutant or wild-type form.Journal of cell science · 2023Article
- Sting and p53 DNA repair pathways are compromised in Alzheimer's disease.Scientific reports · 2023Article
- The dual role of p63 in cancer.Frontiers in oncology · 2023Review
- PRIMA-1 inhibits Y220C p53 amyloid aggregation and synergizes with cisplatin in hepatocellular carcinoma.Frontiers in molecular biosciences · 2023Article
- Transition of amyloid/mutant p53 from tumor suppressor to an oncogene and therapeutic approaches to ameliorate metastasis and cancer stemness.Cancer cell international · 2022Review
- Heterotypic Amyloid β interactions facilitate amyloid assembly and modify amyloid structure.The EMBO journal · 2022Article
- Characterization of full-length p53 aggregates and their kinetics of formation.Biophysical journal · 2022Article
- A role for bioinorganic chemistry in the reactivation of mutant p53 in cancer.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Review
- Potential of rescue and reactivation of tumor suppressor p53 for cancer therapy.Biophysical reviews · 2022Review
- Relevance of Amorphous and Amyloid-Like Aggregates of the p53 Core Domain to Loss of its DNA-Binding Activity.Frontiers in molecular biosciences · 2022Article
- Mesoscopic protein-rich clusters host the nucleation of mutant p53 amyloid fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Destabilized mutant p53s coaggregate with WT p53, p63, and p73 in cancer cell lines. We found that stoichiometric amounts of aggregation-prone mutants induced only small amounts of WT p53 to coaggregate, and preformed aggregates did not significantly seed the aggregation of bulk protein. Similarly, p53 mutants trapped only small amounts of p63 and p73 into their p53 aggregates. Tetrameric full-length protein aggregated at similar rates and kinetics to isolated core domains, but there was some induced aggregation of WT by mutants in hetero-tetramers. p53 aggregation thus differs from the usual formation of amyloid fibril or prion aggregates where tiny amounts of preformed aggregate rapidly seed further aggregation. The proposed aggregation mechanism of p53 of rate-determining sequential unfolding and combination of two molecules accounts for the difference. A molecule of fast-unfolding mutant preferentially reacts with another molecule of mutant and only occasionally traps a slower unfolding WT molecule. The mutant population rapidly self-aggregates before much WT protein is depleted. Subsequently, WT protein self-aggregates at its normal rate. However, the continual production of mutant p53 in a cancer cell would gradually trap more and more WT and other proteins, accounting for the observations of coaggregates in vivo. The mechanism corresponds more to trapping by cross-reaction and coaggregation rather than classical seeding and growth.
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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.