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

• Published in: The Journal of biological chemistry Vol. 280; no. 49; pp. 40450 - 40464
• Main Authors: Hassa, Paul O, Haenni, Sandra S, Buerki, Christine, Meier, Nadja I, Lane, William S, Owen, Heather, Gersbach, Monika, Imhof, Ralph, Hottiger, Michael O
• Format: Journal Article
• Language: English
• Published: United States 09.12.2005
• Subjects: Acetylation; Animals; Cell Cycle Proteins - analysis; Cell Cycle Proteins - physiology; Chemokine CXCL2; Chemokines - genetics; CREB-Binding Protein - metabolism; 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; p300-CBP Transcription Factors; 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
• ISSN: 0021-9258

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.