Transcriptional coactivation of nuclear factor-kappaB-dependent gene expression by p300 is regulated by poly(ADP)-ribose polymerase-1.

Nuclear factor kappaB (NF-kappaB) plays an important role in the transcriptional regulation of genes involved in inflammation and cell survival. In this study, we demonstrated that NF-kappaB-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 ...
alpha (TNFalpha) or lipopolysaccharide (LPS) treatment. PARP-1 and p300 synergistically coactivated NF-kappaB-dependent gene expression in response to TNFalpha and LPS. Furthermore, PARP-1 interacted directly with p300 and enhanced the interaction of NF-kappaB1/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-kappaB by p300 in response to TNFalpha and LPS. Together, these results indicate that PARP-1 acts synergistically with p300 and plays an essential regulatory role in NF-kappaB-dependent gene expression.
Mesh Terms:
Animals, Cell Line, Cell Nucleus, Cell Survival, Cells, Cultured, E1A-Associated p300 Protein, Fibroblasts, Gene Expression Regulation, Enzymologic, Glutathione Transferase, HeLa Cells, Humans, Immunoblotting, Lipopolysaccharides, Mice, Mice, Knockout, Mutation, NF-kappa B, Nuclear Proteins, Plasmids, Poly(ADP-ribose) Polymerases, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Trans-Activators, Transcriptional Activation, Transfection
J. Biol. Chem.
Date: Nov. 14, 2003
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