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

Sayer, John A. and Otto, Edgar A. and O'Toole, John F. and Nurnberg, Gudrun and Kennedy, Michael A. and Becker, Christian and Hennies, Hans Christian and Helou, Juliana and Attanasio, Massimo and Fausett, Blake V. and Utsch, Boris and Khanna, Hemant and Liu, Yan and Drummond, Iain and Kawakami, Isao and Kusakabe, Takehiro and Tsuda, Motoyuki and Ma, Li and Lee, Hwankyu and Larson, Ronald G. and Allen, Susan J. and Wilkinson, Christopher J. and Nigg, Erich A. and Shou, Chengchao and Lillo, Concepcion and Williams, David S. and Hoppe, Bernd and Kemper, Markus J. and Neuhaus, Thomas and Parisi, Melissa A. and Glass, Ian A. and Petry, Marianne and Kispert, Andreas and Gloy, Joachim and Ganner, Athina and Walz, Gerd and Zhu, Xueliang and Goldman, Daniel and Nurnberg, Peter and Swaroop, Anand and Leroux, Michel R. and Hildebrandt, Friedhelm. (2006) The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nature genetics, Vol. 38, H. 6. pp. 674-681.

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Official URL: http://edoc.unibas.ch/dok/A5249352

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The molecular basis of nephronophthisis, 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 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publ
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:19
Deposited On:22 Mar 2012 13:17

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