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

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.
Mesh Terms:
Acetylation, Animals, CREB-Binding Protein, Cell Cycle Proteins, Chemokine CXCL2, Chemokines, Gene Expression Regulation, Histone Acetyltransferases, Macrophages, Mice, Mice, Knockout, NF-kappa B, Nitric Oxide Synthase Type II, Poly(ADP-ribose) Polymerases, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Dec. 09, 2005
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