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Molecular and Cellular Biology, December 1998, p. 7423-7431, Vol. 18, No. 12
Unité de Biologie Moléculaire de
l'Expression Génique,
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.
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
*
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.
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