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Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding
Abstract
Significance: The p53 tumor suppressor is a sequence-specific DNA binding protein that activates gene transcription to regulate cell survival and proliferation. This report investigates the role of the p53 N-terminal transactivation domain in regulating DNA binding affinity and specificity. The results suggest the N-terminal acidic transactivation region of p53 dynamically interacts with the DNA binding domain near residues that contact DNA, thus inhibiting DNA binding and increasing sequence specificity by nucleic acid mimicry or electrostatic shielding. Furthermore, p53 N-terminal–interacting proteins and posttranslational modifications may regulate DNA binding affinity and specificity partly by modulating the N terminus–DNA binding domain interaction.
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“Binding of the DBDs to non-specific DNA, but not to cognate recognition elements, is autoinhibited by dynamic intramolecular interactions between the N-terminal activation domain (NTAD) and the DNA binding surface (Figure 8A).41,72,73”
From Mapping Interactions of the Intrinsically Disordered C-Terminal Regions of Tetrameric p53 by Segmental Isotope Labeling and NMR (2022) · cites this paper as [72]
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Cites
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Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain
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Cited by
Lambourne, L., Mattioli, K., Santoso, C., Sheynkman, G., Inukai, S., Kaundal, B., Berenson, A., Spirohn-Fitzgerald, K., Bhattacharjee, A., Rothman, E., et al. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.03.004 · Cited by 42
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Disordered regions mediate the interaction of p53 and MRE11
Usluer, S., Galhuber, M., Khanna, Y., Bourgeois, B., Spreitzer, E., Michenthaler, H., Prokesch, A., & Madl, T. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2023.119654 · Cited by 9
Metadata
- Authors
- He, F., Borcherds, W., Song, T., Wei, X., Das, M., Chen, L., Daughdrill, G. W., & Chen, J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-04-15
- Volume
- 116
- Issue
- 18
- Pages
- 8859-8868
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 100
- References
- 6
- Language
- en
- Funders
- HHS | NIH | National Cancer Institute (CA141244, CA186917)
- HHS | National Institutes of Health (GM115556)
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- He, F., Borcherds, W., Song, T., Wei, X., Das, M., Chen, L., Daughdrill, G. W., & Chen, J. (2019). Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1903077116
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