DNA-Independent PARP-1 Activation by Phosphorylated ERK2 Increases Elk1 Activity: A Link to Histone Acetylation

Malka Cohen-Armon, Leonid Visochek, Dana Rozensal, Adi Kalal, Ilona Geistrikh, Rodika Klein, Sarit Bendetz-Nezer, Zhong Yao, Rony Seger

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)297-308
Number of pages12
JournalMolecular Cell
Issue number2
StatePublished - 26 Jan 2007


  • DNA


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