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J. Biol. Chem., Vol. 277, Issue 33, 29399-29405, August 16, 2002
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From the Departments of We demonstrate a novel interaction of the
nephroblastoma overexpressed gene (NOV), a member of
the CCN gene family, with the Notch signaling pathway. NOV associates
with the epidermal growth factor-like repeats of Notch1 by the
CT (C-terminal cysteine knot) domain. The promoters of HES1
and HES5, which are the downstream transducers of Notch
signaling, were activated by NOV. Expressions of NOV and
Notch1 were concomitant in the presomitic mesoderm and
later in the myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal cell differentiation. In C2/4 myogenic cells,
elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation. These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis.
The Nephroblastoma Overexpressed Gene (NOV/ccn3) Protein
Associates with Notch1 Extracellular Domain and Inhibits Myoblast
Differentiation via Notch Signaling Pathway*
,,,
,, and**
Molecular Pathology and
¶ Oral Surgery, Graduate School of Tokyo Medical and Dental
University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan, the
§ Laboratory for Cell Function and Dynamics, Advanced
Technology Development Center, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan, and the
Laboratoire d'Oncologie Virale et Moléculaire, UFR de
Biochimie, Université Paris 7-D. Diderot, 75005 Paris,
France
*
This research was supported in part by the Ministry of
Education, Science, Sports and Culture, Japan, a grant-in-aid
for Encouragement of Young Scientists (to K. S.), grants from the
Ligue Nationale contre le Cancer (Comités du Cher et de l'Indre)
(to B. P.), Association pour la Recherche contre le Cancer, and
Groupement des Entreprises Fran
aises dans la Lutte
centre le Cancer (GEFLUC), and grants from the Japan Space Forum
Foundation (to K. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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