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Mol Cell Biol, March 1998, p. 1580-1589, Vol. 18, No. 3
Department of Medicine III, University of
Tokyo School of Medicine, Tokyo, Japan
Received 19 May 1997/Returned for modification 3 August
1997/Accepted 26 November 1997
The Rho family GTP-binding proteins play a critical role in a
variety of cytoskeleton-dependent cell functions. In this study, we
examined the role of Rho family G proteins in muscle differentiation. Dominant negative forms of Rho family proteins and RhoGDI, a GDP dissociation inhibitor, suppressed transcription of muscle-specific genes, while mutationally activated forms of Rho family proteins strongly activated their transcription. C2C12 cells overexpressing RhoGDI (C2C12RhoGDI cells) did not differentiate into myotubes, and
expression levels of myogenin, MRF4, and contractile protein genes but
not MyoD and myf5 genes were markedly reduced in C2C12RhoGDI cells. The
promoter activity of the myogenin gene was suppressed by dominant
negative mutants of Rho family proteins and was reduced in C2C12RhoGDI
cells. Expression of myocyte enhancer binding factor 2 (MEF2), which
has been reported to be required for the expression of the myogenin
gene, was reduced at the mRNA and protein levels in C2C12RhoGDI cells.
These results suggest that the Rho family proteins play a critical role
in muscle differentiation, possibly by regulating the expression of the
myogenin and MEF2 genes.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The Rho Family G Proteins Play a Critical Role in
Muscle Differentiation

*
Corresponding author. Mailing address: Molecular
Cardiology Division, Department of Medicine III, University of Tokyo
School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Phone: 81-33815-5411. Fax: 81-33815-2087. E-mail:
komuro-tky{at}umin.u-tokyo.ac.jp.
Present address: Department of Medicine III, Chiba University
School of Medicine, Chiba, Japan.
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