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