Phosphorylation of NF-kappa B p65 by PKA Stimulates Transcriptional Activity by Promoting a Novel Bivalent Interaction With the Coactivator CBP/p300

Mol Cell. 1998 Apr;1(5):661-71. doi: 10.1016/s1097-2765(00)80066-0.

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