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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
09:45

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity

Published on: January 29, 2018

Crosstalk between JNK and SUMO signaling pathways: deSUMOylation is protective against H2O2-induced cell injury

Marco Feligioni1, Elisa Brambilla, Agata Camassa

  • 1Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy.

Plos One
|December 14, 2011
PubMed
Abstract

Insights

Small ubiquitin-related modifier (SUMO)ylation regulates c-Jun N-terminal kinase (JNK) activation and cell death during oxidative stress. Inhibiting SUMOylation protects against hydrogen peroxide-induced neurotoxicity.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Oxidative stress is implicated in the pathogenesis of neurological disorders, activating pathways that lead to cell death.
  • The interplay between c-Jun N-terminal kinase (JNK) signaling and small ubiquitin-related modifier (SUMO)ylation in response to stress is not well understood.

Purpose of the Study:

  • To investigate the role of SUMOylation in regulating JNK activation and cell death under oxidative stress conditions.
  • To explore the interaction between SUMOylation and JNK signaling in a neuroblastoma cell model.

Main Methods:

  • Utilized a hydrogen peroxide (H(2)O(2))-induced oxidative stress model in neuroblastoma SH-SY5Y cells.
  • Assessed JNK activation, cell death, and the effects of inhibiting JNK (D-JNKI1 peptide) or SUMOylation (SENP1 transfection).
  • Examined the impact of SUMO-1 overexpression on JNK phosphorylation and cell viability.

Main Results:

  • H(2)O(2) induced JNK activation and cell death, which was attenuated by JNK inhibition.
  • SUMO-1 overexpression exacerbated H(2)O(2)-induced cell death, particularly under mild oxidative stress.
  • Inhibition of SUMOylation by SENP1 prevented JNK activation and rescued cells from H(2)O(2)-induced death, suggesting a direct interaction.

Conclusions:

  • SUMOylation plays a significant role in modulating JNK activation during oxidative stress.
  • SUMOylation contributes to cell death pathways activated by oxidative stress.
  • Targeting SUMOylation may offer a therapeutic strategy for neurological disorders involving oxidative stress.

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