The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4

	The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4
	Sayer, JA; Otto, EA; O'Toole, JF; Nurnberg, G; Kennedy, MA; Becker, C; Hennies, HC; Helou, J; Attanasio, M; Fausett, BV
刊名	NATURE GENETICS
	2006
卷号	38 期号:6 页码:674-681
通讯作者	Hildebrandt, F (reprint author), Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.,fhilde@umich.edu
英文摘要	The molecular basis of nephronophthisis(1), the most frequent genetic cause of renal failure in children and young adults, and its association with retinal degeneration and cerebellar vermis aplasia in Joubert syndrome(2) are poorly understood. Using positional cloning, we here identify mutations in the gene CEP290 as causing nephronophthisis. It encodes a protein with several domains also present in CENPF, a protein involved in chromosome segregation. CEP290 ( also known as NPHP6) interacts with and modulates the activity of ATF4, a transcription factor implicated in cAMP-dependent renal cyst formation. NPHP6 is found at centrosomes and in the nucleus of renal epithelial cells in a cell cycle-dependent manner and in connecting cilia of photoreceptors. Abrogation of its function in zebrafish recapitulates the renal, retinal and cerebellar phenotypes of Joubert syndrome. Our findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis of cystic kidney disease, retinal degeneration, and central nervous system development.
学科主题	Genetics & Heredity
类目[WOS]	Genetics & Heredity
关键词[WOS]	PRIMARY CILIA ; RETINITIS-PIGMENTOSA ; DOMAIN PROTEIN ; NEPHRONOPHTHISIS ; GENE ; INVERSIN ; MUTATIONS ; INTERACTS ; ENCODES ; DISEASE
收录类别	SCI
语种	英语
WOS记录号	WOS:000237954800022
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1731]
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	Sayer, JA,Otto, EA,O'Toole, JF,et al. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4[J]. NATURE GENETICS,2006,38(6):674-681.
APA	Sayer, JA.,Otto, EA.,O'Toole, JF.,Nurnberg, G.,Kennedy, MA.,...&Hildebrandt, F.(2006).The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4.NATURE GENETICS,38(6),674-681.
MLA	Sayer, JA,et al."The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4".NATURE GENETICS 38.6(2006):674-681.