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Updated: Feb 3, 2026
Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
Methods to Screen Compounds Against Mutant p53 Misfolding and Aggregation for Cancer Therapeutics
Giulia Diniz da Silva Ferretti1,2, Danielly C Ferraz da Costa2,3, Jerson L Silva4,5
1Instituto de Bioquímica Médica Leopoldo de Meis, UFRJ, Rio de Janeiro, Brazil.
Abstract:
p53 is a critical tumor suppressor that functions as a transcription factor. Mutations in the TP53 gene are observed in more than 50% of cancer cases worldwide. Several of these mutations lead to a less stable, aggregation-prone protein that accumulates in cancer cells. These mutations are associated with a gain of oncogenic function, which leads to cancer progression. p53 amyloid aggregation is a common feature in most of these mutants; thus, it can be used as a druggable target to reactivate or induce the degradation of p53 and promote a retraction in the aggressive pattern of mutant p53-containing cells. We show here a series of experiments for the screening and validation of new p53 antiamyloid compounds.
Insights
Mutant p53 protein aggregation in cancer can be targeted. New compounds were screened and validated to disrupt these amyloid structures, offering a potential therapeutic strategy against aggressive cancers.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The p53 protein is a crucial tumor suppressor, acting as a transcription factor.
- Mutations in the TP53 gene occur in over 50% of human cancers.
- Many TP53 mutations result in an unstable, aggregation-prone p53 protein that drives cancer progression.
Purpose of the Study:
- To identify and validate novel compounds targeting p53 amyloid aggregation.
- To explore the therapeutic potential of disrupting mutant p53 aggregation in cancer cells.
Main Methods:
- Screening of potential anti-amyloid compounds.
- Validation of identified compounds for their efficacy against p53 aggregation.
Main Results:
- Demonstration of a series of experiments for screening and validation.
- Identification of compounds capable of targeting p53 amyloid aggregation.
Conclusions:
- p53 amyloid aggregation is a druggable target in mutant p53 cancers.
- Targeting p53 aggregation may offer a new strategy to combat cancer progression and reduce the aggressive phenotype of mutant p53-containing cells.
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