Regulation of the p300 HAT domain via a novel activation loop
Abstract
The transcriptional coactivator p300 is a histone acetyltransferase (HAT) whose function is critical for regulating gene expression in mammalian cells. However, the molecular events that regulate p300 HAT activity are poorly understood. We evaluated autoacetylation of the p300 HAT protein domain to determine its function. Using expressed protein ligation, the p300 HAT protein domain was generated in hypoacetylated form and found to have reduced catalytic activity. This basal catalytic rate was stimulated by autoacetylation of several key lysine sites within an apparent activation loop motif. This post-translational modification and catalytic regulation of p300 HAT activity is conceptually analogous to the activation of most protein kinases by autophosphorylation. We therefore propose that this autoregulatory loop could influence the impact of p300 on a wide variety of signaling and transcriptional events.
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p300 possesses histone acetyltransferase (HAT) activity.
“p300 possesses histone acetyltransferase (HAT) activity (Thompson et al., 2004).”
From Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1 (2011) · cites this paper as Thompson et al., 2004
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- Authors
- Thompson, P. R., Wang, D., Wang, L., Fulco, M., Pediconi, N., Zhang, D., An, W., Ge, Q., Roeder, R. G., Wong, J., Levrero, M., Sartorelli, V., Cotter, R. J., & Cole, P. A.
- Affiliations
- Johns Hopkins University (US)
- National Institutes of Health (US)
- Policlinico Umberto I (IT)
- Baylor College of Medicine (US)
- Rockefeller University (US)
- Cell Signaling Technology (United States) (US)
- Corresponding author
- Cole, Philip A
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2004-03-07
- Volume
- 11
- Issue
- 4
- Pages
- 308-315
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2074129822
- Cited by
- 423
- References
- 36
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 17 · 2023: 19 · 2022: 24 · 2021: 23 · 2020: 22 · 2019: 16 · 2018: 22 · 2017: 22 · 2016: 26 · 2015: 25 · 2014: 22 · 2013: 16 · 2012: 23
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) (submittedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Ellison Medical Foundation
- Johns Hopkins University
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- P300, histone acetyltransferase, activation loop, lysine acetylation, post-translational modification, transcriptional coactivator, expressed protein ligation
- MeSH terms
- Acetyl Coenzyme A, Acetylation, Acetyltransferases, Amino Acid Sequence, Animals, Cloning, Molecular, Enzyme Activation, Escherichia coli, Kinetics, Molecular Sequence Data, Recombinant Proteins, Gene Expression Regulation, Enzymologic, Sequence Alignment, Conserved Sequence, Sequence Homology, Amino Acid, DNA Primers, Escherichia coli Proteins, Histone Acetyltransferases
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