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Bifunctional ligand design for modulating mutant p53 aggregation in cancer
Abstract
Iodination of a bifunctional ligand framework restores p53 function by interacting with and inhibiting mutant p53 aggregation.
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“L1 and LH adjust mutant p53 aggregation by increasing zinc ion levels in cells and promoting interactions between zinc ions and mutant p53.”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [349]
In the citing paper
“LI and LH acted as metallochaperones binding to zinc ions, which increased the intracellular zinc ion level and improved the binding ability of zinc ions to mutant p53, thus regulating mutant p53 aggregation.”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [499]
In the citing paper
“LI and LH also increased the expression of Noxa and p21 by 1.5 to 4.3-fold. Meanwhile, transmission electron microscopy observation confirmed that mutant p53 could significantly inhibit the formation of aggregates when cocultured with LI.499”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [499]
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Citations
Cites
The amyloid state and its association with protein misfolding diseases.
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Transcriptional control of human p53-regulated genes
Riley, T., Sontag, E., Chen, P., & Levine, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2395 · Cited by 1,921
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities
Muller, P. A. J., & Vousden, K. H. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.021 · Cited by 1,545
Organoids as an in vitro model of human development and disease
Fatehullah, A., Tan, S. H., & Barker, N. (2016) · Nature Cell Biology · doi:10.1038/ncb3312 · Cited by 1,508
Prion-like transmission of protein aggregates in neurodegenerative diseases
Brundin, P., Melki, R., & Kopito, R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2873 · Cited by 778
The complexity of p53 stabilization and activation
Lavin, M. F., & Gueven, N. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401925 · Cited by 701
Small-Molecule Fluorescent Sensors for Investigating Zinc Metalloneurochemistry
Nolan, E. M., & Lippard, S. J. (2009) · Accounts of Chemical Research · doi:10.1021/ar8001409 · Cited by 620
A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas
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., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.002 · Cited by 341
Choi, J.-S., Braymer, J. J., Nanga, R. P. R., Ramamoorthy, A., & Lim, M. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006091107 · Cited by 264
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Cited by
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016
p53: from understanding its structure to advances in therapeutic targeting
Wang, W., Liu, X., Liu, H., Abolhassani, H., Yan, H., Zhang, H., & Wang, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02549-5 · Cited by 30
Metadata
- Authors
- Miller, J. J., Blanchet, A., Orvain, C., Nouchikian, L., Reviriot, Y., Clarke, R. M., Martelino, D., Wilson, D., Gaiddon, C., & Storr, T.
- Venue
- Chemical Science
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2019
- Volume
- 10
- Issue
- 46
- Pages
- 10802-10814
- ISSN
- 2041-6520
- 2041-6539
- Cited by
- 41
- References
- 15
- Language
- en
- Funders
- Michael Smith Foundation for Health Research
- Natural Sciences and Engineering Research Council of Canada
- Simon Fraser University
- Centre National de la Recherche Scientifique
- Institut National de la Santé et de la Recherche Médicale
- Association pour la Recherche sur le Cancer
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- Miller, J. J., Blanchet, A., Orvain, C., Nouchikian, L., Reviriot, Y., Clarke, R. M., Martelino, D., Wilson, D., Gaiddon, C., & Storr, T. (2019). Bifunctional ligand design for modulating mutant p53 aggregation in cancer. Chemical Science. https://doi.org/10.1039/c9sc04151f
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