Crosstalk between JNK and SUMO signaling pathways: DeSUMOylation is protective against H 2O 2-induced cell injury

Marco Feligioni, Elisa Brambilla, Agata Camassa, Alessandra Sclip, Andrea Arnaboldi, Federica Morelli, Xanthi Antoniou, Tiziana Borsello

Research output: Contribution to journalArticle

Abstract

Background: Oxidative stress is a key feature in the pathogenesis of several neurological disorders. Following oxidative stress stimuli a wide range of pathways are activated and contribute to cellular death. The mechanism that couples c-Jun N-terminal kinase (JNK) signaling, a key pathway in stress conditions, to the small ubiquitin-related modifier (SUMO), an emerging protein in the field, is largely unknown. Methodology/Principal Findings: With this study we investigated if SUMOylation participates in the regulation of JNK activation as well as cellular death in a model of H 2O 2 induced-oxidative stress. Our data show that H 2O 2 modulates JNK activation and induces cellular death in neuroblastoma SH-SY5Y cells. Inhibition of JNK's action with the D-JNKI1 peptide rescued cells from death. Following H 2O 2, SUMO-1 over-expression increased phosphorylation of JNK and exacerbated cell death, although only in conditions of mild oxidative stress. Furthermore inhibition of SUMOylation, following transfection with SENP1, interfered with JNK activation and rescued cells from H 2O 2 induced death. Importantly, in our model, direct interaction between these proteins can occur. Conclusions/Significance: Taken together our results show that SUMOylation may significantly contribute to modulation of JNK activation and contribute to cell death in oxidative stress conditions.

Original languageEnglish
Article numbere28185
JournalPLoS One
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Feligioni, M., Brambilla, E., Camassa, A., Sclip, A., Arnaboldi, A., Morelli, F., Antoniou, X., & Borsello, T. (2011). Crosstalk between JNK and SUMO signaling pathways: DeSUMOylation is protective against H 2O 2-induced cell injury. PLoS One, 6(12), [e28185]. https://doi.org/10.1371/journal.pone.0028185