title: A fast signal-induced activation of Poly(ADP-ribose) polymerase: a novel downstream target of phospholipase c.
abstract: 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-Ca(2+) 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.
authors.affiliation: The Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Homburg
authors.forename: L
authors.initials: L
authors.lastname: Visochek
authors.forename: N
authors.initials: N
authors.lastname: Moran
authors.forename: F
authors.initials: F
authors.lastname: Dantzer
authors.forename: E
authors.initials: E
authors.lastname: Priel
authors.forename: E
authors.initials: E
authors.lastname: Asculai
authors.forename: D
authors.initials: D
authors.lastname: Schwartz
authors.forename: V
authors.initials: V
authors.lastname: Rotter
authors.forename: N
authors.initials: N
authors.lastname: Dekel
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Armon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D004249:DNA Damage / Q000502:physiology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D009687:Nuclear Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D015544:Inositol 1,4,5-Trisphosphate; D011065:Poly(ADP-ribose) Polymerases; D010738:Type C Phospholipases; D004264:DNA Topoisomerases, Type I; D002118:Calcium