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Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site
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“Notably, ATO administration can rescue a wide range of structural p53 mutants, including R175H, R175L, G245S, and R249S, but it cannot exert the same function in DNA contact mutants, such as R248Q and R273H.344”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [344]
In the citing paper
“Complex structures show that MQ can bind to six of the ten cysteines,425 while ATO431 and PAT432 bind at a pocket formed by Cys124, Cys135, Cys141 and Met133.”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [431]
In the citing paper
“Most structural p53 mutants were rescued to varying degrees by ATO, but mutations in the DNA contact surface (R248Q, R273H) were not observed.”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [431]
In the citing paper
“The crystal structure showed that the DNA-binding domains of Cys124, Cys135, Cys141 and Met133 formed an As-binding pocket, with direct interaction of arsenic with Cys124, Cys135 and Cys141 and van der Waals forces between the side chain of Met133 and the arsenic atom (Fig. 9c).”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [431]
In the citing paper
“Lu Min’s team found that ATO could help stabilize the structural mutation of p53 (R175H) and restore the cancer suppressive activity of p53.431”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [431]
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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
Mutant p53 in cancer: from molecular mechanism to therapeutic modulation
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Drugs Targeting p53 Mutations with FDA Approval and in Clinical Trials
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Metadata
- Authors
- Chen, S., Wu, J.-L., Liang, Y., Tang, Y.-G., Song, H.-X., Wu, L.-L., Xing, Y.-F., Yan, N., Li, Y.-T., Wang, Z.-Y., Xiao, S.-J., Lu, X., Chen, S.-J., & Lu, M.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 39
- Issue
- 2
- Pages
- 225-239.e8
- ISSN
- 1535-6108
- Cited by
- 241
- References
- 15
- Language
- en
- Update notices
- erratum (2025-08-11)
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
- Funders
- Program of Shanghai Academic Research Leader (20XD1422700)
- National Key Research and Development Program of China (2017YFA0506200)
- National Natural Science Foundation of China (2018CR006, 81861130368, 82073292, 81622002)
- Shanghai Municipal Education Commission
- Ludwig Institute for Cancer Research
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- Chen, S., Wu, J.-L., Liang, Y., Tang, Y.-G., Song, H.-X., Wu, L.-L., Xing, Y.-F., Yan, N., Li, Y.-T., Wang, Z.-Y., Xiao, S.-J., Lu, X., Chen, S.-J., & Lu, M. (2021). Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site. Cancer Cell. https://doi.org/10.1016/j.ccell.2020.11.013
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