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.

FEBS Letters
|January 27, 2009
PubMed

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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