Oxidative stress-enhanced SUMOylation and aggregation of ataxin-1: Implication of JNK pathway

Joohyun Ryu, Sayeon Cho, Byoung Chul Park, Do Hee Lee

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Although the polyglutamine protein ataxin-1 is modified by SUMO at multiple sites, the functions of such modification or how it is regulated are still unknown. Here we report that SUMO-1 or Ubc9 over-expression stimulated the aggregation of ataxin-1 and that oxidative stress, such as hydrogen peroxide treatment, further enhanced SUMO conjugation and aggregation of ataxin-1. Accordingly, co-treatment with antioxidant N-acetyl-cysteine attenuated the effect of oxidative stress. Ataxin-1, which can activate c-Jun N-terminal kinase (JNK) pathway by itself, strongly associated with apoptosis signal-regulating kinase 1 (ASK1) while not interacting with JNK. Finally, treatment of JNK-specific inhibitor caused a reduction in the oxidant-enhanced SUMOylation and aggregation of ataxin-1. Together these results indicate that SUMO modification of ataxin-1 promotes the aggregation of ataxin-1 and that oxidative stress and JNK pathway play roles in this process.

Original languageEnglish (US)
Pages (from-to)280-285
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume393
Issue number2
DOIs
StatePublished - Mar 5 2010
Externally publishedYes

Keywords

  • ASK1
  • Ataxin-1
  • JNK
  • Oxidative stress
  • Polyglutamine diseases
  • SUMO-1

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