期刊
NEUROSCIENCE LETTERS
卷 440, 期 1, 页码 4-8出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.05.052
关键词
Nrdp1; Parkin; E3 ligase; ubiquitination; reactive oxidative stress
Parkin plays an important role in the pathogenesis of Parkinson's disease. We previously described that Nrdp1, a RING-finger ubiquitin E3 ligase, interacted with Parkin by the yeast two-hybrid assay and by c( immunoprecipitation. Here we further demonstrated that overexpression of Nrdp1 significantly reduced the enclogenous Parkin level in an Nrdp1 dosage-dependent and proteasome-dependent manner. More importantly, Nrdp1 ubiquitinated Parkin and catalyzed the poly-ubiquitin chains on Parkin in vitro as well as in cells, indicating Parkin is an Nrdp1 substrate. In addition, we demonstrated that overexpression of Nrdp1 increased the production of reactive oxygen species (ROS), which was abrogated by co-expression of Parkin. Conversely, suppression of Nrdp1 by shRNA conferred SH-SY5Y cells a lower ROS level. Together, we provided evidence that interactions between Nrdp1 and Parkin negatively regulated Parkin level and affected ROS production, suggesting that Nrdp1 may play a role in Parkinson's disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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