Your browser version may not work well with NCBI's Web applications. More information here...
1: Science. 2004 May 28;304(5675):1328-31. Epub 2004 Apr 22.Click here to read Links
Comment in:
Science. 2004 Jun 25;304(5679):1905; author reply 1905.
Science. 2005 Jun 24;308(5730):1870; author reply 1870.

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

Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.

PMID: 15105460 [PubMed - indexed for MEDLINE]