Regulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch.

2.50
Hdl Handle:
http://hdl.handle.net/10541/73080
Title:
Regulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch.
Authors:
Flasza, Marzena; Nguyen Huu, Ngoc Sa; Mazaleyrat, Sabine; Clémence, Sylvaine; Villemant, Cécile; Clarke, Robert B; Baron, M
Abstract:
Nedd4 family ubiquitin ligases regulate trafficking and degradation of numerous target substrates in different cellular compartments, including at the plasma membrane, in endosomes, in the secretory pathway and in the nucleus. WWP1 is a Nedd4 family protein closely related to mouse Itch and Drosophila Su(dx), both of which have been shown to regulate the Notch receptor. To investigate the possibility that WWP1 is also associated with Notch signalling we coexpressed human Notch1 and WWP1 in mouse myoblast cells. We found that WWP1 could localize to both the nucleus and cytoplasm in a context dependent manner. Coexpression of human Notch1 (hN1) depleted WWP1 from the nucleus to colocalise with hN1 in early endosomes, dependent on the presence of the C-terminal HECT domain. Furthermore we found that full-length expressed WWP1 could interact in vitro with the cytoplasmic domain of human Notch1. The Notch receptor has multiple roles in development, mediating a short-range signal that controls cell fate and pattern formation. The canonical Notch signal involves proteolytic release of the soluble Notch intracellular domain and the activation by the latter of the transcription factor Suppressor of Hairless/CBF-1 in the nucleus. This pathway does not however account for all of the activity of Notch. The ability of Notch to regulate the nuclear localization of WWP1 suggests a possible alternative mechanism by which Notch may communicate a signal to the nucleus. Drosophila Notch similarly regulated the nuclear localization of the Drosophila Nedd4 family protein, Suppressor of deltex, implying conservation of this mechanism during evolution.
Affiliation:
University of Manchester, Faculty of Life Sciences, Michael Smith Building, Manchester.
Citation:
Regulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch., 23 (3):269-76 Mol. Membr. Biol.
Journal:
Molecular Membrane Biology
Issue Date:
2006
URI:
http://hdl.handle.net/10541/73080
DOI:
10.1080/09687860600665010
PubMed ID:
16785210
Type:
Article
Language:
en
ISSN:
0968-7688
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorFlasza, Marzena-
dc.contributor.authorNguyen Huu, Ngoc Sa-
dc.contributor.authorMazaleyrat, Sabine-
dc.contributor.authorClémence, Sylvaine-
dc.contributor.authorVillemant, Cécile-
dc.contributor.authorClarke, Robert B-
dc.contributor.authorBaron, M-
dc.date.accessioned2009-07-09T12:24:42Z-
dc.date.available2009-07-09T12:24:42Z-
dc.date.issued2006-
dc.identifier.citationRegulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch., 23 (3):269-76 Mol. Membr. Biol.en
dc.identifier.issn0968-7688-
dc.identifier.pmid16785210-
dc.identifier.doi10.1080/09687860600665010-
dc.identifier.urihttp://hdl.handle.net/10541/73080-
dc.description.abstractNedd4 family ubiquitin ligases regulate trafficking and degradation of numerous target substrates in different cellular compartments, including at the plasma membrane, in endosomes, in the secretory pathway and in the nucleus. WWP1 is a Nedd4 family protein closely related to mouse Itch and Drosophila Su(dx), both of which have been shown to regulate the Notch receptor. To investigate the possibility that WWP1 is also associated with Notch signalling we coexpressed human Notch1 and WWP1 in mouse myoblast cells. We found that WWP1 could localize to both the nucleus and cytoplasm in a context dependent manner. Coexpression of human Notch1 (hN1) depleted WWP1 from the nucleus to colocalise with hN1 in early endosomes, dependent on the presence of the C-terminal HECT domain. Furthermore we found that full-length expressed WWP1 could interact in vitro with the cytoplasmic domain of human Notch1. The Notch receptor has multiple roles in development, mediating a short-range signal that controls cell fate and pattern formation. The canonical Notch signal involves proteolytic release of the soluble Notch intracellular domain and the activation by the latter of the transcription factor Suppressor of Hairless/CBF-1 in the nucleus. This pathway does not however account for all of the activity of Notch. The ability of Notch to regulate the nuclear localization of WWP1 suggests a possible alternative mechanism by which Notch may communicate a signal to the nucleus. Drosophila Notch similarly regulated the nuclear localization of the Drosophila Nedd4 family protein, Suppressor of deltex, implying conservation of this mechanism during evolution.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCell Compartmentation-
dc.subject.meshCell Nucleolus-
dc.subject.meshCells, Cultured-
dc.subject.meshDrosophila-
dc.subject.meshDrosophila Proteins-
dc.subject.meshEndosomes-
dc.subject.meshHumans-
dc.subject.meshMice-
dc.subject.meshNuclear Localization Signals-
dc.subject.meshProtein Structure, Tertiary-
dc.subject.meshProtein Transport-
dc.subject.meshReceptor, Notch1-
dc.subject.meshUbiquitin-Protein Ligases-
dc.titleRegulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch.en
dc.typeArticleen
dc.contributor.departmentUniversity of Manchester, Faculty of Life Sciences, Michael Smith Building, Manchester.en
dc.identifier.journalMolecular Membrane Biologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.