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Originally published in Science Express on 22 April 2004
Science 28 May 2004:
Vol. 304. no. 5675, pp. 1328 - 1331
DOI: 10.1126/science.1093891
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Reports

S-Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function

Kenny K. K. Chung,1,2 Bobby Thomas,1,2 Xiaojie Li,1,2 Olga Pletnikova,3 Juan C. Troncoso,2,3 Laura Marsh,2,4 Valina L. Dawson,1,2,5,6 Ted M. Dawson1,2,5*

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.

1 Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4 Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
6 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* To whom correspondence should be addressed. E-mail: tdawson{at}jhmi.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)