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A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas
Open accessAbstract
Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs.
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“Peptide ReACp53 was described to prevent the amyloid-like aggregation of proteins with point mutations in p53-R248Q or p53-R175H.”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [134]
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“Treatment of ovarian cancer xenografts with ReACp53 resulted in decreased cell proliferation and tumor reduction [134].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [134]
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Metadata
- Authors
- Soragni, A., Janzen, D. M., Johnson, L. M., Lindgren, A. G., Thai-Quynh Nguyen, A., Tiourin, E., Soriaga, A. B., Lu, J., Jiang, L., Faull, K. F., Pellegrini, M., Memarzadeh, S., & Eisenberg, D. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- Corresponding author
- Memarzadeh, Sanaz
- Eisenberg, David S.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 29
- Issue
- 1
- Pages
- 90-103
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4733364
- OpenAlex
- W2207474307
- Cited by
- 341
- References
- 61
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 29 · 2023: 31 · 2022: 42 · 2021: 29 · 2020: 32 · 2019: 35 · 2018: 39 · 2017: 33 · 2016: 28
- FWCI
- 13.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (1S10RR023718-01A2, AG-029430, R01CA183877)
- Pardee Foundation
- National Center for Advancing Translational Science (UL1TR000124)
- American Cancer Society (RSG-14-217-01-TBG)
- National Science Foundation (MCB 0958111)
- Jonsson Cancer Center Foundation
- Lynne Cohen Foundation
- Phase One Foundation
- Ovarian Cancer Circle Inspired by Robin Babbini
- Leath L. and Marcia L. Millen Family Fund
- G.O. Discovery Lab Foundation
- HHMI
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, amyloid-like aggregation, p53 missense mutations, cell-penetrating peptides, high-grade serous ovarian cancer, organoids, xenografts, cell proliferation, apoptosis
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Disease Models, Animal, Female, Humans, Mice, Transgenic, Ovarian Neoplasms, Tumor Suppressor Protein p53, Cell Proliferation
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