The Nephroblastoma Overexpressed Gene (NOV/ccn3) Protein Associates with Notch1 Extracellular Domain and Inhibits Myoblast Differentiation via Notch Signaling Pathway

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 HES1and HES5, whi...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-08, Vol.277 (33), p.29399-29405
Main Authors: Sakamoto, Kei, Yamaguchi, Shunji, Ando, R., Miyawaki, Atsushi, Kabasawa, Yuji, Takagi, Minoru, Li, Chang Long, Perbal, Bernard, Katsube, Ken-ichi
Format: Article
Language:English
Subjects:
Animals
Blotting, Northern
Blotting, Western
Calcium - metabolism
Cell Differentiation - physiology
Cell Line
Connective Tissue Growth Factor
Humans
Immediate-Early Proteins
Intercellular Signaling Peptides and Proteins
Membrane Proteins - metabolism
Mice
Muscles - cytology
Nephroblastoma Overexpressed Protein
Oncogene Proteins, Viral - metabolism
Oncogene Proteins, Viral - physiology
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins - physiology
Receptor, Notch1
Receptors, Cell Surface
Signal Transduction
Transcription Factors
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Summary: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 HES1and 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 MyoDand 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M203727200