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.