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 language | English (US) |
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Pages (from-to) | 280-285 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 393 |
Issue number | 2 |
DOIs | |
State | Published - Mar 5 2010 |
Externally published | Yes |
Bibliographical note
Funding Information:We are grateful to Prof. Chin Ha Chung for providing HA-tagged SUMO-1 construct and to Jung Young Choi and Jeong Hee Ryu for their assistance. This study was supported by a special research grant from Seoul Women’s University (2009) to Do Hee Lee and the grant of Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea ( BGC0300912 ) to Byoung Chul Park.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
Keywords
- ASK1
- Ataxin-1
- JNK
- Oxidative stress
- Polyglutamine diseases
- SUMO-1