Phosphorylation of NF-κB p65 by PKA Stimulates Transcriptional Activity by Promoting a Novel Bivalent Interaction with the Coactivator CBP/p300
Open accessAbstract
The transcriptional activity of NF-kappa B is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase A (PKA). The transcriptional coactivator CPB/p300 associates with NF-kappa B p65 through two sites, an N-terminal domain that interacts with the C-terminal region of unphosphorylated p65, and a second domain that only interacts with p65 phosphorylated on serine 276. Accessibility to both sites is blocked in unphosphorylated p65 through an intramolecular masking of the N terminus by the C-terminal region of p65. Phosphorylation by PKA both weakens the interaction between the N- and C-terminal regions of p65 and creates an additional site for interaction with CBP/p300. Therefore, PKA regulates the transcriptional activity of NF-kappa B by modulating its interaction with CBP/p300.
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NF-κB is able to recruit p300/CBP to chromatin and to increase H3K27ac.
“Moreover, NF-κB is able both to recruit p300/CBP to chromatin53 and to increase H3K27ac54, 55.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [53]
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- Authors
- Zhong, H., Voll, R. E., & Ghosh, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ghosh, Sankar
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 1
- Issue
- 5
- Pages
- 661-671
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1985118687
- Cited by
- 1,210
- References
- 2
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 19 · 2023: 15 · 2022: 18 · 2021: 29 · 2020: 17 · 2019: 26 · 2018: 31 · 2017: 23 · 2016: 33 · 2015: 34 · 2014: 42 · 2013: 37 · 2012: 41
- FWCI
- 25.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (RO1 AI 33443)
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- NF-κB p65, protein kinase A, CBP/p300, transcriptional coactivator, transcriptional regulation, protein-protein interaction, C-terminal domain
- MeSH terms
- p300-CBP-Associated Factor, Acetyltransferases, Amino Acid Sequence, DNA-Binding Proteins, Humans, Molecular Sequence Data, Nuclear Proteins, Peptide Fragments, Peptide Mapping, Phosphorylation, Promoter Regions, Genetic, Serine, Transcription Factors, Yeasts, Transcriptional Activation, Trans-Activators, NF-kappa B, Protein Structure, Tertiary, Cyclic AMP-Dependent Protein Kinases, Cell Cycle Proteins, Jurkat Cells, Saccharomyces cerevisiae Proteins, p300-CBP Transcription Factors, CREB-Binding Protein, Histone Acetyltransferases, Transcription Factor RelA, Nuclear Receptor Coactivator 3
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