S-nitrosylation of Parkin regulates ubiquitination and compromises Parkin's protective function

被引：635

作者：

Chung, KKK

Thomas, B

Li, XJ

Pletnikova, O

Troncoso, JC

Marsh, L

Dawson, VL

Dawson, TM ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

来源：

SCIENCE | 2004年 / 304卷 / 5675期

关键词：

D O I：

10.1126/science.1093891

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Parkin is an E3 ubiquitin ligase involved in the ubiquitination of proteins that are important in the survival of dopamine neurons in Parkinson's disease (PD). We show that parkin is S-nitrosylated in vitro, as well as in vivo in a mouse model of PD and in brains of patients with PD and diffuse Lewy body disease. Moreover, S-nitrosylation inhibits parkin's ubiquitin E3 ligase activity and its protective function. The inhibition of parkin's ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in these disorders by impairing the ubiquitination of parkin substrates.

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页码：1328 / 1331

页数：4

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