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.
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Acknowledgments
We thank the Brazilian funding agencies CAPES, CNPq, FAPERJ, Fundação do Câncer and Serrapilheira Institute for the support.
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Ferretti, G.D., da Costa, D.C.F., L. Silva, J., Pereira Rangel, L. (2019). Methods to Screen Compounds Against Mutant p53 Misfolding and Aggregation for Cancer Therapeutics. In: Gomes, C. (eds) Protein Misfolding Diseases. Methods in Molecular Biology, vol 1873. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8820-4_17
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DOI: https://doi.org/10.1007/978-1-4939-8820-4_17
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