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Updated: Jun 26, 2026

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
Regulation of the activity and expression of ERK8 by DNA damage
Iva V Klevernic1, Niall M B Martin, Philip Cohen
1MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH Scotland, UK.
Abstract:
We have investigated the agonists that activate transfected extracellular signal-regulated kinase 8 (ERK8) in cells, and have found that the most potent activators are hydrogen peroxide, DNA alkylating and cross-linking agents and the poly (ADP-ribose) polymerase inhibitor KU-0058948. The feature shared by all these agents is that they lead to the accumulation of single strand breaks in DNA, suggesting a role for ERK8 in the response to, or repair of, DNA single strand breaks. The DNA alkylating agent MMS also induced the disappearance of endogenous ERK8 by a proteasome-dependent mechanism.
Insights
Extracellular signal-regulated kinase 8 (ERK8) is activated by agents causing DNA single-strand breaks. This suggests ERK8 plays a role in DNA damage response and repair pathways.
Area of Science:
- Molecular Biology
- Cellular Signaling
- DNA Damage Response
Background:
- Extracellular signal-regulated kinase 8 (ERK8) is a kinase involved in cellular processes.
- The specific activators and functions of ERK8 in response to cellular stress are not fully understood.
Purpose of the Study:
- To identify agonists that activate transfected extracellular signal-regulated kinase 8 (ERK8) in cells.
- To elucidate the role of ERK8 in the cellular response to DNA damage.
Main Methods:
- Transfection of cells with ERK8.
- Treatment with hydrogen peroxide, DNA alkylating/cross-linking agents, and poly (ADP-ribose) polymerase inhibitor KU-0058948.
- Analysis of ERK8 activation and endogenous ERK8 levels.
Main Results:
- Hydrogen peroxide, DNA alkylating/cross-linking agents, and KU-0058948 were identified as potent activators of ERK8.
- These agents induce the accumulation of DNA single-strand breaks.
- Methyl methanesulfonate (MMS) treatment led to proteasome-dependent degradation of endogenous ERK8.
Conclusions:
- ERK8 activation is linked to the presence of DNA single-strand breaks.
- ERK8 likely plays a role in the cellular response to, or repair of, DNA single-strand breaks.
- DNA damage can also lead to the degradation of ERK8 via proteasomal pathways.
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