title: Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron.
abstract: Mammalian neuronal cells abundantly express a deubiquitylating enzyme, ubiquitin carboxy-terminal hydrolase 1 (UCH L1). Mutations in UCH L1 are linked to Parkinson's disease as well as gracile axonal dystrophy (gad) in mice. In contrast to the UCH L3 isozyme that is universally expressed in all tissues, UCH L1 is expressed exclusively in neurons and testis/ovary. We found that UCH L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life. The gad mouse, in which the function of UCH L1 is lost, exhibited a reduced level of monoubiquitin in neurons. In contrast, overexpression of UCH L1 caused an increase in the level of ubiquitin in both cultured cells and mice. These data suggest that UCH L1, with avidity and affinity for ubiquitin, insures ubiquitin stability within neurons. This study is the first to show the function of UCH L1 in vivo.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Yu-Lai
authors.initials: YL
authors.lastname: Wang
authors.forename: Koji
authors.initials: K
authors.lastname: Takada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takizawa
authors.forename: Rieko
authors.initials: R
authors.lastname: Setsuie
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Yae
authors.initials: Y
authors.lastname: Sato
authors.forename: Kaori
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Sun
authors.forename: Mikako
authors.initials: M
authors.lastname: Sakurai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kimura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Namikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Aoki
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D017353:Gene Deletion; D051379:Mice / Q000235:genetics; D008817:Mice, Mutant Strains; D009474:Neurons / Q000201:enzymology*; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D043222:Ubiquitin Thiolesterase