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Cell Growth & Differentiation Vol. 10, 295-306, May 1999
© 1999 American Association for Cancer Research

p53 Is a Transcriptional Activator of the Muscle-specific Phosphoglycerate Mutase Gene and Contributesin Vivo to the Control of Its Cardiac Expression1

Pilar Ruiz-Lozano, Mary L. Hixon, Mark W. Wagner, Ana I. Flores, Shuntaro Ikawa, Albert S. Baldwin, Jr., Kenneth R. Chien and Antonio Gualberto2

Departments of Physiology and Biophysics [P. R-L., M. W. W., A. I. F., A. G.] and Genetics [M. L. H.], Case Western Reserve University School of Medicine, Cleveland, Ohio 44106; Department of Medicine and Center for Molecular Genetics, University of California at San Diego, California 92093 [P. R-L., K. R. C.]; Department of Cell Biology, IDAC, Tohoku University, Sendai, Japan 980 [S. I.]; and Lineberger Comprehensive Cancer Center and Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599 [A. S. B.]

The role that the p53 tumor suppressor gene product plays in cellular differentiation remains controversial. However, recent evidence indicates that p53 is required for proper embryogenesis. We have studied the effect of p53 on the expression mediated by the promoter of the rat muscle-specific phosphoglycerate mutase gene (M-PGAM), a marker for cardiac and skeletal muscle differentiation. Experiments involving transient transfection, mobility shift assay, and site-directed mutagenesis demonstrated that p53 specifically binds and transactivates the M-PGAM promoter. The p53-related proteins p51A and p73L also transactivated M-PGAM. Moreover, stable expression of a p53 dominant mutant in C2C12 cells blocked the induction of M-PGAM expression during the myoblast to myotube transition and the ability of p53, p51A, and p73L to transactivate the M-PGAM promoter. In addition, impaired expression of M-PGAM was observed in a subset of p53-null animals in heart and muscle tissues of anterior-ventral location. These results demonstrate that p53 is a transcriptional activator of M-PGAM that contributes in vivo to the control of its cardiac expression. These data support previous findings indicating a role for p53 in cellular differentiation.




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Copyright © 1999 by the American Association of Cancer Research.