P53 protein is activated during muscle differentiation and participates with MyoD in the transcription of muscle creatine kinase gene.

Abstract

The p53 protein is a transcription factor involved in processes of cell growth and differentiation. The muscle creatine kinase (MCK) gene whose transcription is induced during muscle differentiation contains p53-binding sites. In this study we tested the involvement of p53 in the activation of MCK transcription during muscle differentiation of C2 cells. We have shown that the p53 protein is stabilized and its DNA binding and transcriptional activities are induced during muscle differentiation. At the stage of muscle-differentiation, p53 protein can induce the accurate transcription of a minimal p53-dependent MCK reporter gene. Moreover, p53 cooperates with MyoD in the induction of MCK transcription. The expression of a dominant negative p53 protein in muscle cells reduced the expression of endogenous MCK gene. The dominant negative p53 protein abolished the cooperativity of wild type p53 with MyoD. Amino and carboxy terminal residues of MyoD required for the cooperation with p53 in transcription were identified. The cooperativity between the two proteins occurs also at the stage of DNA binding. We suggest that p53 protein is activated during myoblast differentiation and participates with MyoD in the induction of MCK transcription.