Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron

被引：320

作者：

Osaka, H

Wang, YL

Takada, K

Takizawa, S

Setsuie, R

Li, H

Sato, Y

Nishikawa, K

Sun, YJ

Sakurai, M

Harada, T

Hara, Y

Kimura, I

Chiba, S

Namikawa, K

Kiyama, H

Noda, M

Aoki, S

Wada, K ^{[1
]}

机构：

[1] NCNP, Natl Inst Neurosci, Dept Degenerat Neurol Dis, Tokyo 1878502, Japan

[2] Japan Sci & Technol Corp, PRESTO, Informat & Cellular Funct, Kawaguchi, Saitama 3320012, Japan

[3] Jikei Univ, Sch Med, Dept Biochem 1, Minato Ku, Tokyo 1058461, Japan

[4] Asahikawa Med Coll, Dept Psychiat & Neurol, Asahikawa, Hokkaido 0788510, Japan

[5] Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Pathophysiol, Higashi Ku, Fukuoka 8128582, Japan

[6] Waseda Univ, Sch Human Sci, Dept Basic Human Sci, Tokorozawa, Saitama 3591192, Japan

[7] Osaka City Univ, Grad Sch Med, Dept Anat & Neurobiol, Abeno Ku, Osaka 5458585, Japan

来源：

HUMAN MOLECULAR GENETICS | 2003年 / 12卷 / 16期

关键词：

D O I：

10.1093/hmg/ddg211

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1945 / 1958

页数：14

共 38 条

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