Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation

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	Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation
	Zhou, Jiawei
刊名	HUMAN MOLECULAR GENETICS
	2009
卷号	18 期号:22 页码:4268-4281
关键词	AMYOTROPHIC-LATERAL-SCLEROSIS RETICULUM-ASSOCIATED DEGRADATION MOTOR-NEURON DEATH TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN-QUALITY CONTROL MACHADO-JOSEPH-DISEASE CELL-RECEPTOR SUBUNITS N-TERMINAL HUNTINGTIN LINKED MUTANT SOD1 HMG-COA REDUCTASE
ISSN号	0964-6906
通讯作者	Wang, GH (reprint author), Univ Sci & Technol China, Lab Mol Neuropathol, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China,wghui@ustc.edu.cn
英文摘要	Superoxide dismutase-1 (SOD1) and ataxin-3 are two neurodegenerative disease proteins in association with familial amyotrophic lateral sclerosis and Machado-Joseph disease/spinocerebellar ataxia type 3. Both normal and mutant types of SOD1 and ataxin-3 are degraded by the proteasome. It was recently reported that these two proteins are associated with the endoplasmic reticulum (ER). Mammalian gp78 is an E3 ubiquitin ligase involved in ER-associated degradation (ERAD). Here, we show that gp78 interacts with both SOD1 and ataxin-3. Overexpression of gp78 promotes the ubiquitination and degradation of these two proteins, whereas knockdown of gp78 stabilizes them. Moreover, gp78 represses aggregate formation of mutant SOD1 and protect cells against mutant SOD1-induced cell death. Furthermore, gp78 is increased in cells transfected with these two mutant proteins as well as in ALS mice. Thus, our results suggest that gp78 functions in the regulation of SOD1 and ataxin-3 to target them for ERAD.
学科主题	Biochemistry & Molecular Biology ; Genetics & Heredity
收录类别	SCI
资助信息	National Natural Sciences Foundation of China[30770664]; National Hightech Research and Development program of China 973-projects[2006CB500703]; 863-project[2006AA02A408]; CAS Knowledge Innovation Project[KSCX2-YWR-138]; Bureau of Education of Anhui[ZD2008008-2]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1628]
专题	上海神经科学研究所_神经所(总) 上海神经科学研究所_基底神经节的发育与退行性疾病研究组
推荐引用方式 GB/T 7714	Zhou, Jiawei. Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation[J]. HUMAN MOLECULAR GENETICS,2009,18(22):4268-4281.
APA	Zhou, Jiawei.(2009).Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation.HUMAN MOLECULAR GENETICS,18(22),4268-4281.
MLA	Zhou, Jiawei."Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation".HUMAN MOLECULAR GENETICS 18.22(2009):4268-4281.