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Recognition of the disordered p53 transactivation domain by the transcriptional adapter zinc finger domains of CREB-binding protein
Abstract
Significance: The tumor suppressor p53 regulates the cellular response to genomic damage by recruiting the transcriptional coactivator cyclic-AMP response element-binding protein (CREB)-binding protein (CBP) and its paralog p300 to activate stress response genes. We report NMR structures of the complexes formed between the full-length, intrinsically disordered N-terminal transactivation domain of p53 and the transcriptional adapter zinc finger domains (TAZ1 and TAZ2) of CBP. Exchange broadening of NMR spectra of the complexes was ameliorated by using fusion proteins and segmental isotope labeling. The structures show how the p53 transactivation domain uses bipartite binding motifs to recognize diverse partners, reveal the critical interactions required for high affinity binding, and provide insights into the mechanism by which phosphorylation enhances the ability of p53 to recruit CBP and p300.
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“the narrow linewidths for residues in the NLS and CTD (Figure 2), and also residues in the N-terminal activation domain,63 show that these domains are highly dynamic in the full-length p53 tetramer.”
From Mapping Interactions of the Intrinsically Disordered C-Terminal Regions of Tetrameric p53 by Segmental Isotope Labeling and NMR (2022) · cites this paper as [63]
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Intrinsically unstructured proteins and their functions
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Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206
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Goodman, R. H., & Smolik, S. (2000) · Genes & Development · doi:10.1101/gad.14.13.1553 · Cited by 1,778
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204
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p300/MDM2 complexes participate in MDM2-mediated p53 degradation
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Self-citation
Metadata
- Authors
- Krois, A. S., Ferreon, J. C., Martinez-Yamout, M. A., Dyson, H. J., & Wright, P. E.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-03-14
- Volume
- 113
- Issue
- 13
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 117
- References
- 9
- Language
- en
- Funders
- HHS | National Institutes of Health (CA096865)
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