title: S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function.
abstract: 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.
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Kenny K K
authors.initials: KK
authors.lastname: Chung
authors.forename: Bobby
authors.initials: B
authors.lastname: Thomas
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: Laura
authors.initials: L
authors.lastname: Marsh
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D016923:Cell Death; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020961:Lewy Body Disease / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D051843:Synucleins; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D011994:Recombinant Proteins; C118958:SNCAIP protein, human; C498464:Sncaip protein, mouse; D051843:Synucleins; D025801:Ubiquitin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein