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Mol Cell Biol, February 1998, p. 1074-1083, Vol. 18, No. 2
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Increase in p202 Expression during Skeletal Muscle Differentiation: Inhibition of MyoD Protein Expression and Activity by p202dagger

Bansidhar Datta,Dagger Wang Min,§ Sandeep Burma,par and Peter Lengyel*

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520

Received 22 October 1997/Accepted 13 November 1997

p202 is a primarily nuclear, interferon-inducible murine protein that is encoded by the Ifi 202 gene. Overexpression of p202 in transfected cells retards cell proliferation. p202 modulates the pattern of gene expression by inhibiting the activity of various transcription factors including NF-kappa B, c-Fos, c-Jun, E2F-1, and p53. Here we report that p202 was constitutively expressed in mouse skeletal muscle and that the levels of 202 RNA and p202 greatly increased during the differentiation of cultured C2C12 myoblasts to myotubes. When overexpressed in transfected myoblasts, p202 inhibited the expression of one muscle protein (MyoD) without affecting the expression of a second one (myogenin). Thus, the decrease in the level of MyoD (but not of myogenin) during muscle differentiation may be the consequence of the increase in p202 level. Overexpressed p202 also inhibited the transcriptional activity of both MyoD and myogenin. This inhibition was correlated with an interaction of p202 with both proteins, as well as the inhibition by p202 of the sequence-specific binding of both proteins to DNA. This inhibition of the expression of MyoD and of the transcriptional activity of MyoD and myogenin may account for the inhibition of the induction of myoblast differentiation by premature overexpression of p202.

* Corresponding author. Mailing address: Yale University, Department of Molecular Biophysics and Biochemistry, P.O. Box 208024, 333 Cedar St., New Haven, CT 06520-8024. Phone: (203) 737-2061. Fax: (203) 785-6404. E-mail: Peter.Lengyel{at}Yale.edu.

dagger B.D. and P.L. dedicate this study to the memory of Naba K. Gupta.

Dagger Present address: Department of Chemistry, University of Nebraska at Lincoln, Lincoln, NE 68588.

§ Present address: Genemedicine, The Woodlands, TX 77381.

par Present address: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802.




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