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J. Biol. Chem., Vol. 278, Issue 46, 45145-45153, November 14, 2003

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Transcriptional Coactivation of Nuclear Factor-B-dependent Gene Expression by p300 Is Regulated by Poly(ADP)-ribose Polymerase-1^*

Paul O. Hassa, Christine Buerki, Cornelia Lombardi, Ralph Imhof, and Michael O. Hottiger

From the Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland

Nuclear factor B (NF-B) plays an important role in the transcriptional regulation of genes involved in inflammation and cell survival. In this study, we demonstrated that NF-B-dependent gene expression was inhibited by E1A in poly(ADP)-ribose polymerase-1 knock out (PARP-1 (–/–)) cells complemented with wild type PARP-1 after tumor necrosis factor (TNF) or lipopolysaccharide (LPS) treatment. PARP-1 and p300 synergistically coactivated NF-B-dependent gene expression in response to TNF and LPS. Furthermore, PARP-1 interacted directly with p300 and enhanced the interaction of NF-B1/p50 to p300. The C terminus, harboring the catalytic domain of PARP-1 but not its enzymatic activity, was required for complete transcriptional coactivation of NF-B by p300 in response to TNF and LPS. Together, these results indicate that PARP-1 acts synergistically with p300 and plays an essential regulatory role in NF-B-dependent gene expression.

Received for publication, July 22, 2003 , and in revised form, August 25, 2003.

^* This work was supported in part by Novartis as part of the ZNZ/Novartis Research Collaboration, and the Swiss National Science Foundation Grant 3100-67771.02 (to P. O. H. and C. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the Kanton of Zurich.

To whom correspondence should be addressed. Tel.: 41-1-635-54-74; Fax: 41-1-635-68-40; E-mail: hottiger{at}vetbio.unizh.ch.

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