DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation.

PolyADP-ribose polymerases (PARPs) catalyze a posttranslational modification of nuclear proteins by polyADP-ribosylation. The catalytic activity of the abundant nuclear protein PARP-1 is stimulated by DNA strand breaks, and PARP-1 activation is required for initiation of DNA repair. Here we show that PARP-1 also acts within extracellular signal-regulated kinase (ERK) signaling ...
cascade that mediates growth and differentiation. The findings reveal an alternative mode of PARP-1 activation, which does not involve binding to DNA or DNA damage. In a cell-free system, recombinant PARP-1 was intensively activated and thereby polyADP-ribosylated by a direct interaction with phosphorylated ERK2, and the activated PARP-1 dramatically increased ERK2-catalyzed phosphorylation of the transcription factor Elk1. In cortical neurons treated with nerve growth factors and in stimulated cardiomyocytes, PARP-1 activation enhanced ERK-induced Elk1-phosphorylation, core histone acetylation, and transcription of the Elk1-target gene c-fos. These findings constitute evidence for PARP-1 activity within the ERK signal-transduction pathway.
Mesh Terms:
Acetylation, Animals, Base Sequence, Brain, Cell Nucleus, Cell-Free System, Cells, Cultured, DNA, Enzyme Activation, Gene Expression, Genes, fos, Histones, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 1, Models, Biological, Phosphorylation, Poly(ADP-ribose) Polymerases, RNA, Small Interfering, Rats, Rats, Sprague-Dawley, Recombinant Proteins, ets-Domain Protein Elk-1
Mol. Cell
Date: Jan. 26, 2007
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