A role of poly (ADP-ribose) polymerase in NF-kappaB transcriptional activation.
The transcription factor NF-kappaB plays a critical role in immune and inflammatory responses. Here we show that poly (ADP ribose) polymerase (PARP) is required for specific NF-kappaB transcriptional activation in vivo. The activation of the HIV-LTR promoter and an NF-kappaB-dependent artificial promoter was drastically reduced in PARP (-/-) cells, independently of the signaling pathway through which NF-kappaB was induced. Furthermore NF-kappaB-dependent gene activation was restored in vivo by the expression of PARP in PARP (-/-) cells. Finally, we show that both NF-kappaB and PARP formed a stable immunoprecipitable nuclear complex. This interaction did not need DNA binding. Our results suggest that PARP is an important cofactor in the activation cascade of NF-kappaB-dependent target genes.
Hassa
P O
PO
Institute of Veterinary Biochemistry, University of Zürich, Switzerland.
Hottiger
M O
MO
D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases