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.
Hassa
Paul O
PO
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Buerki
Christine
C
Lombardi
Cornelia
C
Imhof
Ralph
R
Hottiger
Michael O
MO
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D008070:Lipopolysaccharides; D016328:NF-kappa B; D009687:Nuclear Proteins; D015534:Trans-Activators; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase