MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jarriault, S.
Right arrow Articles by Israël, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jarriault, S.
Right arrow Articles by Israël, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 1998, p. 7423-7431, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Delta-1 Activation of Notch-1 Signaling Results in HES-1 Transactivation

Sophie Jarriault,1 Odile Le Bail,1 Estelle Hirsinger,2 Olivier Pourquié,2 Frédérique Logeat,1 Clare F. Strong,1 Christel Brou,1 Nabil G. Seidah,3 and Alain Israël1,*

Unité de Biologie Moléculaire de l'Expression Génique, URA 1773 CNRS, Institut Pasteur, 75724 Paris Cedex 15,1 and Institut de Biologie du Développement de Marseille (IBDM), LGPD-UMR CNRS 9943, Campus de Luminy, 13288 Marseille Cedex 09,2 France, and J. A. DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institut of Montreal, Montreal, Quebec H2W 1R7, Canada3

Received 19 March 1998/Returned for modification 18 May 1998/Accepted 1 September 1998

The Notch receptor is involved in many cell fate determination events in vertebrates and invertebrates. It has been shown in Drosophila melanogaster that Delta-dependent Notch signaling activates the transcription factor Suppressor of Hairless, leading to an increased expression of the Enhancer of Split genes. Genetic evidence has also implicated the kuzbanian gene, which encodes a disintegrin metalloprotease, in the Notch signaling pathway. By using a two-cell coculture assay, we show here that vertebrate Dl-1 activates the Notch-1 cascade. Consistent with previous data obtained with active forms of Notch-1 a HES-1-derived promoter construct is transactivated in cells expressing Notch-1 in response to Dl-1 stimulation. Impairing the proteolytic maturation of the full-length receptor leads to a decrease in HES-1 transactivation, further supporting the hypothesis that only mature processed Notch is expressed at the cell surface and activated by its ligand. Furthermore, we observed that Dl-1-induced HES-1 transactivation was dependent both on Kuzbanian and RBP-J activities, consistent with the involvement of these two proteins in Notch signaling in Drosophila. We also observed that exposure of Notch-1-expressing cells to Dl-1 results in an increased level of endogenous HES-1 mRNA. Finally, coculture of Dl-1-expressing cells with myogenic C2 cells suppresses differentiation of C2 cells into myotubes, as previously demonstrated for Jagged-1 and Jagged-2, and also leads to an increased level of endogenous HES-1 mRNA. Thus, Dl-1 behaves as a functional ligand for Notch-1 and has the same ability to suppress cell differentiation as the Jagged proteins do.

* Corresponding author. Mailing address: Unité de Biologie Moléculaire de l'Expression Génique, URA 1773 CNRS, Institut Pasteur, 25 rue de Dr Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45 68 85 53. Fax: (33) 1 40 61 30 40. E-mail: aisrael{at}pasteur.fr.

Molecular and Cellular Biology, December 1998, p. 7423-7431, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1998 by the American Society for Microbiology. All rights reserved.