Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
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.
Zhong
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Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Voll
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Ghosh
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D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006801:Humans; D019169:Jurkat Cells / Q000737:chemistry / Q000201:enzymology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D010446:Peptide Fragments / Q000494:pharmacology; D010449:Peptide Mapping; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000502:physiology; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D015003:Yeasts / Q000235:genetics; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D016328:NF-kappa B; D009687:Nuclear Proteins; D056921:Nuclear Receptor Coactivator 3; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C052130:GAL4 protein, S cerevisiae; C494363:CREBBP protein, human; C538866:NCOA3 protein, human