Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology

	Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology
	Yang, H; Li, JJ; Liu, S; Zhao, J; Jiang, YJ; Song, AX; Hu, HY
刊名	SCIENTIFIC REPORTS
	2014
卷号	4 期号:1 页码:6410-6410
通讯作者	Hu, HY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,hyhu@sibcb.ac.cn
英文摘要	Expansion of polyglutamine (polyQ) tract may cause protein misfolding and aggregation that lead to cytotoxicity and neurodegeneration, but the underlying mechanism remains to be elucidated. We applied ataxin-3 (Atx3), a polyQ tract-containing protein, as a model to study sequestration of normal cellular proteins. We found that the aggregates formed by polyQ-expanded Atx3 sequester its interacting partners, such as P97/VCP and ubiquitin conjugates, into the protein inclusions through specific interactions both in vitro and in cells. Moreover, this specific sequestration impairs the normal cellular function of P97 in down-regulating neddylation. However, expansion of polyQ tract in Atx3 does not alter the conformation of its surrounding regions and the interaction affinities with the interacting partners, although it indeed facilitates misfolding and aggregation of the Atx3 protein. Thus, we propose a loss-of-function pathology for polyQ diseases that sequestration of the cellular essential proteins via specific interactions into inclusions by the polyQ aggregates causes dysfunction of the corresponding proteins, and consequently leads to neurodegeneration.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	MACHADO-JOSEPH-DISEASE ; SPINOCEREBELLAR ATAXIA ; NEURODEGENERATIVE DISEASES ; INTRANUCLEAR INCLUSIONS ; NEURONAL INTRANUCLEAR ; UBIQUITIN-BINDING ; GLUTAMINE REPEATS ; BODY FORMATION ; PROTEIN ; HUNTINGTIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000341942200002
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/288]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yang, H,Li, JJ,Liu, S,et al. Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology[J]. SCIENTIFIC REPORTS,2014,4(1):6410-6410.
APA	Yang, H.,Li, JJ.,Liu, S.,Zhao, J.,Jiang, YJ.,...&Hu, HY.(2014).Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology.SCIENTIFIC REPORTS,4(1),6410-6410.
MLA	Yang, H,et al."Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology".SCIENTIFIC REPORTS 4.1(2014):6410-6410.