Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription

J Biol Chem. 2005 Dec 9;280(49):40450-64. doi: 10.1074/jbc.M507553200. Epub 2005 Oct 4.

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) and nuclear factor kappaB (NF-kappaB) have both been demonstrated to play a pathophysiological role in a number of inflammatory disorders. We recently presented evidence that PARP-1 can act as a promoter-specific coactivator of NF-kappaB in vivo independent of its enzymatic activity. PARP-1 directly interacts with p300 and both subunits of NF-kappaB (p65 and p50) and synergistically coactivates NF-kappaB-dependent transcription. Here we show that PARP-1 is acetylated in vivo at specific lysine residues by p300/CREB-binding protein upon stimulation. Furthermore, acetylation of PARP-1 at these residues is required for the interaction of PARP-1 with p50 and synergistic coactivation of NF-kappaB by p300 and the Mediator complex in response to inflammatory stimuli. PARP-1 physically interacts with the Mediator. Interestingly, PARP-1 interacts in vivo with histone deacetylases (HDACs) 1-3 but not with HDACs 4-6 and might be deacetylated in vivo by HDACs 1-3. Thus, acetylation of PARP-1 by p300/CREB-binding protein plays an important regulatory role in NF-kappaB-dependent gene activation by enhancing its functional interaction with p300 and the Mediator complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • CREB-Binding Protein / metabolism*
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / physiology
  • Chemokine CXCL2
  • Chemokines / genetics
  • Gene Expression Regulation / physiology*
  • Histone Acetyltransferases / analysis
  • Histone Acetyltransferases / physiology
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • NF-kappa B / pharmacology
  • NF-kappa B / physiology*
  • Nitric Oxide Synthase Type II / genetics
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / deficiency
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Promoter Regions, Genetic / genetics
  • Transcription Factors / analysis
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • NF-kappa B
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases