Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

	Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)
	Jiang, YJ; Che, MX; Yuan, JQ; Xie, YY; Yan, XZ; Hu, HY
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2011
卷号	286 期号:28 页码:25236-25245
通讯作者	Hu, HY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,hyhu@sibs.ac.cn
英文摘要	Huntington disease (HD) is an autosomal inherited disorder that causes the deterioration of brain cells. The polyglutamine (polyQ) expansion of huntingtin (Htt) is implicated in the pathogenesis of HD via interaction with an RNA splicing factor, Htt yeast two-hybrid protein A/forming-binding protein 11 (HYPA/FBP11). Besides the pathogenic polyQ expansion, Htt also contains a proline-rich region (PRR) located exactly in the C terminus to the polyQ tract. However, how the polyQ expansion influences the PRR-mediated protein interaction and how this abnormal interaction leads to the biological consequence remain elusive. Our NMR structural analysis indicates that the PRR motif of Htt cooperatively interacts with the tandem WW domains of HYPA through domain chaperoning effect of WW1 on WW2. The polyQ-expanded Htt sequesters HYPA to the cytosolic location and then significantly reduces the efficiency of pre-mRNA splicing. We propose that the toxic gain-of-function of the polyQ-expanded Htt that causes dysfunction of cellular RNA processing contributes to the pathogenesis of HD.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TANDEM WW DOMAINS ; PROLINE-RICH REGION ; LIGAND RECOGNITION ; GROUP-II/III ; IN-VIVO ; DISEASE ; AGGREGATION ; BINDING ; PATHOGENESIS ; SPECIFICITY
收录类别	SCI
语种	英语
WOS记录号	WOS:000292547900069
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/886]
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	Jiang, YJ,Che, MX,Yuan, JQ,et al. Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(28):25236-25245.
APA	Jiang, YJ,Che, MX,Yuan, JQ,Xie, YY,Yan, XZ,&Hu, HY.(2011).Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA).JOURNAL OF BIOLOGICAL CHEMISTRY,286(28),25236-25245.
MLA	Jiang, YJ,et al."Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)".JOURNAL OF BIOLOGICAL CHEMISTRY 286.28(2011):25236-25245.