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

. 2005 Dec 9;280(49):40450-64.

doi: 10.1074/jbc.M507553200. Epub 2005 Oct 4.

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

Paul O Hassa et al. J Biol Chem. 2005.

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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.

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