A fast signal-induced activation of poly(ADP-ribose) polymerase: A novel downstream target of phospholipase C

We present the first evidence for a fast activation of the nuclear protein poly(ADP-ribose) polymerase (PARP) by signals evoked in the cell membrane, constituting a novel mode of signaling to the cell nucleus. PARP, an abunda nt, highly conserved, chromatin-bound protein found only in eukaryotes, exc lusively catalyzes polyADP-ribosylation of DNA-binding proteins, thereby mo dulating their activity. Activation of PARP, reportedly induced by formatio n of DNA breaks, is involved in DNA transcription, replication, and repair. Our findings demonstrate an alternative mechanism: a fast activation of PA RP, evoked by inositol 1,4,5,-trisphosphate-Ca2+ mobilization. that does no t involve DNA breaks. These findings identify PARP as a novel downstream ta rget of phospholipase C, and unveil a novel fast signal-induced modificatio n of DNA-binding proteins by poly ADP-ribosylation.