A Fast Signal–Induced Activation of Poly(Adp-Ribose) Polymerase

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–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.

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

“…In regard to what is known about the intracellular stimuli of PARP1, at least two signaling pathways, an increased intracellular Ca 2+ level and the activation of ERK1/2, have been found to activate PARP1 during hypertrophy [140,141]. By analysis of PARP-inhibitors, it was found that PARP activates the TEF1-mediated gene transcription from the M-CAT sites [136].…”

Epigenetic Treatments for Cognitive Impairments

“…Likewise, poly-ADP ribosylation is reversed by poly (ADPribose)glycohydrolase (Quenet et al, 2009). Interestingly, although poly-ADP ribosylation and PARP1 activity are most well known for their role in DNA repair following damage, PARP1 activation has been shown to increase in cortical neurons following depolarization (Homburg et al, 2000). Likewise, PARP1 is required for long-term synaptic facilitation and long-term memory in aplysia, suggesting a functional role in the nervous system (Cohen-Armon et al, 2004;Hernandez et al, 2009).…”

Histone H1 Poly[ADP]-Ribosylation Regulates the Chromatin Alterations Required for Learning Consolidation

“…Poly[ADP-ribose] polymerase 1 (PARP-1) is activated by stressful stimuli that damage DNA (Virág and Szabó , 2002), although it can also be induced by other physiological stimuli. Depolarization and exposure of cortical neurons to neuronal growth factor have been shown to activate PARP-1 in the absence of DNA damage (Homburg et al, 2000;Visochek et al, 2005). Moreover, it was shown recently that PARP-1 activation is required for long-term neuronal plasticity in Aplysia and mice (Cohen-Armon et al, 2004;Goldberg et al, 2009;Hernández et al, 2009).…”