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Published online 24 July 2000. doi:10.1083/jcb.150.2.293
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© The Rockefeller University Press, 0021-9525/2000/7/293/ $5.00
The Journal of Cell Biology, Volume 150, Number 2, July 24, 2000 293-308

Original Article

A Fast Signal–induced Activation of Poly(ADP-ribose) Polymerase: A Novel Downstream Target of Phospholipase C

S. Homburga, L. Visocheka, N. Moranb, F. Dantzerc, E. Prield, E. Asculaid, D. Schwartze, V. Rottere, N. Dekela, and M. Cohen-Armona
a The Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
b Department of Agricultural Botany, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot 76100, Israel
c Laboratory of Molecular and Structural Biology, Ecole Superieure de Biotechnologie de Strasbourg, F-67400 Illkirch-Graffenstaden, France
d Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva 84105, Israel
e Department of Molecular and Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

Correspondence to: M. Cohen-Armon, Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel. Tel:972-3-535-4865 Fax:972-3-535-1139 E-mail:marmon{at}post.tau.ac.il.

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 abundant, highly conserved, chromatin-bound protein found only in eukaryotes, exclusively catalyzes polyADP-ribosylation of DNA-binding proteins, thereby modulating their activity. Activation of PARP, reportedly induced by formation of DNA breaks, is involved in DNA transcription, replication, and repair. Our findings demonstrate an alternative mechanism: a fast activation of PARP, evoked by inositol 1,4,5,-trisphosphate–Ca2+ mobilization, that does not involve DNA breaks. These findings identify PARP as a novel downstream target of phospholipase C, and unveil a novel fast signal–induced modification of DNA-binding proteins by polyADP-ribosylation.

Key Words: poly(ADP-ribose) polymerase, calcium signaling, inositol 1,4,5-trisphosphate, electrical stimulation, brain neurons


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