Sci. Aging Knowl. Environ., 28 April 2004
Vol. 2004, Issue 17, p. or11


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

Kenny K. K. Chung, Ted M. Dawson, Bobby Thomas, Xiaojie Li, Olga Pletnikova, Juan C. Troncoso, Laura Marsh, and Valina L. Dawson

Abstract: Science 22 April 2004 (10.1126/science.1093891) (Science Express Reports)

Parkin is an E3 ubiquitin ligase, which is involved in the ubiquitination of proteins that are important in the survival of dopamine neurons in Parkinson's disease (PD). Here we show that parkin is S-nitrosylated in vitro, and in vivo in the MPTP animal 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 and parkin's protective function.


Science of Aging Knowledge Environment. ISSN 1539-6150