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 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.
Homburg
S
S
The Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Visochek
L
L
Moran
N
N
Dantzer
F
F
Priel
E
E
Asculai
E
E
Schwartz
D
D
Rotter
V
V
Dekel
N
N
Cohen-Armon
M
M
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*
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