DNA-Independent PARP-1 Activation by Phosphorylated ERK2 Increases Elk1 Activity: A Link to Histone Acetylation
Open accessAbstract
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.
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PARP1 activation can be induced by stress responses other than DNA damage, including ERK-1, Notch/HES-1, and intracellular calcium overload.
“In addition, as reviewed by Weaver and Yang 94, PARP1 activation can be induced by stress responses other than DNA damage, including the ERK-1 95, 96 and Notch/HES-1 97 signaling pathways and intracellular calcium overload 98.”
From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [96]
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BackgroundA macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation
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Self-citation
- Authors
- Cohen-Armon, M., Visochek, L., Rozensal, D., Kalal, A., Geistrikh, I., Klein, R., Bendetz-Nezer, S., Yao, Z., & Seger, R.
- Affiliations
- Tel Aviv University (IL)
- Bar-Ilan University (IL)
- Weizmann Institute of Science (IL)
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 25
- Issue
- 2
- Pages
- 297-308
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2001233441
- Cited by
- 329
- References
- 39
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 18 · 2023: 11 · 2022: 19 · 2021: 16 · 2020: 13 · 2019: 12 · 2018: 13 · 2017: 13 · 2016: 18 · 2015: 23 · 2014: 19 · 2013: 20 · 2012: 25
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2389 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- PARP1, ERK2, Elk-1, histone acetylation, poly(ADP-ribosyl)ation, ERK signaling, transcriptional regulation, c-fos, nerve growth factor, cardiomyocytes, cortical neurons
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Poly (ADP-Ribose) Polymerase-1, Acetylation, Animals, Base Sequence, Brain, Cell Nucleus, Cell-Free System, Cells, Cultured, DNA, Enzyme Activation, Histones, Models, Biological, Phosphorylation, Poly(ADP-ribose) Polymerases, Recombinant Proteins, Gene Expression, Genes, fos, Rats, Sprague-Dawley, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, RNA, Small Interfering, ets-Domain Protein Elk-1, Rats, In Vitro Techniques
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