Nature Cell Biology 7, 1191 - 1201 (2005)
Published online: 13 November 2005; | doi:10.1038/ncb1327
There is an Erratum (December 2005) associated with this Article.
Regulation of Notch signalling by non-visual  -arrestinAshim Mukherjee1, 6, Alexey Veraksa1, 2, 6, Andreas Bauer3, Carine Rosse4, Jacques Camonis4
& Spyros Artavanis-Tsakonas1, 51
Department of Cell Biology, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA. 2
Present address: Biology Department, University of Massachusetts Boston, Boston, MA 02125, USA. 3
Cellzome AG, Heidelberg 69117, Germany. 4
Institut Curie, Inserm U-528, 75248 Paris Cedex 05, France. 5
Collège de France, 11 place Marcelin Berthelot, 75231, Paris, Cedex 05, France. 6
These authors contributed equally to this work.
Correspondence should be addressed to Spyros Artavanis-Tsakonas tsakonas@helix.mgh.harvard.edu Signalling activity of the Notch receptor, which plays a fundamental role in metazoan cell fate determination, is controlled at multiple levels. We uncovered a Notch signal-controlling mechanism that depends on the ability of the non-visual  -arrestin, Kurtz (Krz), to influence the degradation and, consequently, the function of the Notch receptor. We identified Krz as a binding partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the existence of a trimeric Notch–Dx–Krz protein complex. This complex mediates the degradation of the Notch receptor through a ubiquitination-dependent pathway. Our results establish a novel mode of regulation of Notch signalling and define a new function for non-visual -arrestins.
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