Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetyltransferases / genetics
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Acetyltransferases / metabolism
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Amino Acid Sequence
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CREB-Binding Protein
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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DNA-Binding Proteins
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Histone Acetyltransferases
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Humans
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Jurkat Cells / chemistry
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Jurkat Cells / enzymology
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Molecular Sequence Data
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NF-kappa B / chemistry
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism
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Nuclear Receptor Coactivator 3
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Peptide Fragments / pharmacology
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Peptide Mapping
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Phosphorylation
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Promoter Regions, Genetic / physiology
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Protein Structure, Tertiary
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Saccharomyces cerevisiae Proteins*
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Serine / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factor RelA
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation / drug effects
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Transcriptional Activation / physiology*
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Yeasts / genetics
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p300-CBP Transcription Factors
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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GAL4 protein, S cerevisiae
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NF-kappa B
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Nuclear Proteins
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Peptide Fragments
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factor RelA
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Transcription Factors
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Serine
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Acetyltransferases
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CREB-Binding Protein
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CREBBP protein, human
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Histone Acetyltransferases
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NCOA3 protein, human
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Nuclear Receptor Coactivator 3
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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Cyclic AMP-Dependent Protein Kinases