泛素
生物
基因剔除小鼠
脱氮酶
细胞生物学
热休克蛋白27
骨骼肌
体内
热休克蛋白70
热休克蛋白
生物化学
内分泌学
基因
遗传学
作者
Rieko Setsuie,Mari Suzuki,Yukihiro Tsuchiya,Keiji Wada
标识
DOI:10.1016/j.neuint.2010.03.021
摘要
Ubiquitin C-terminal hydrolase (UCH)-L3 is an enzyme with a strongly suggested de-ubiquitinating function by in vitro studies, but has poorly been investigated in vivo. In this study, we show that skeletal muscles of Uchl3−/− mice exhibit the up-regulation of cleaved ATF6, Grp78, and PDI as well as HSP27, HSP70, HSP90 and HSP110, which indicate the induction of stress responses. The prominent accumulation of polyubiquitinated proteins, one of the factors reported to induce stress responses, was observed in the skeletal muscle of Uchl3−/− mice. Mouse embryonic fibroblasts (MEFs) from Uchl3−/− mice also showed an accumulation of polyubiquitinated proteins. Moreover, the polyubiquitinated protein accumulation in Uchl3−/− MEFs was attenuated by the exogenous expression of wild-type, but not hydrolase activity deficient, UCH-L3. In addition, wild-type, but not its hydrolase activity or ubiquitin binding activity deficient UCH-L3 showed the ability to cleave ubiquitin from polyubiquitinated lysozyme in vitro. These results suggest that UCH-L3 functions as a de-ubiquitinating enzyme in vivo where lack of its hydrolase activity may result in the prominent accumulation of ubiquitinated proteins and subsequent induction of stress responses in skeletal muscle.
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