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Recognition of the disordered p53 transactivation domain by the transcriptional adapter zinc finger domains of CREB-binding protein

Krois, Alexander S., Ferreon, Josephine C., Martinez-Yamout, Maria A., Dyson, H. Jane, Wright, Peter E.·2016·Proceedings of the National Academy of Sciences

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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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
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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Krois, A. S., Ferreon, J. C., Martinez-Yamout, M. A., Dyson, H. J., & Wright, P. E. (2016). Recognition of the disordered p53 transactivation domain by the transcriptional adapter zinc finger domains of CREB-binding protein. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1602487113

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