p53 is a transcriptional activator of the muscle-specific phosphoglyceratemutase gene and contributes in vivo to the control of its cardiac expression

The role that the p53 tumor suppressor gene product plays in cellular diffe rentiation remains controversial. However, recent evidence indicates that p 53 is required for proper embryogenesis. We have studied the effect of p53 on the expression mediated by the promoter of the rat muscle-specific phosp hoglycerate mutase gene (M-PGAM), a marker for cardiac and skeletal muscle differentiation. Experiments involving transient transfection, mobility shi ft 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 d uring 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 i s a transcriptional activator of M-PGAM that contributes in vivo to the con trol of its cardiac expression. These data support previous findings indica ting a role for p53 in cellular differentiation.