| dc.description.abstract | The overexpression of p53 has been known widely to be stimulated by cellular stress; however, its aberrant towards muscle development that leads to muscle disease is not apparent. Therefore, we are investigating how p53 or M3-p53, a chimeric gene of p53 and the activation domain of MyoD, affects cell cycle, metabolism, and muscle differentiation in myoblast. Up-regulation of both genes exhibited interchangeable results. The over-activation of p53 caused cell cycle progression to arrest at G1/G0, increased oxidative stress, decreased cell viability, and up-regulated p21 and Rb1. Intriguingly, Cyclin D was not repressed. Meanwhile, M3-p53 induction also exhibited similar results. It arrested cell cycle at G0/G1, reduced cell number, and up-regulated oxidative stress, p21, and Rb1 but slightly induced cyclin D. We also explored the effects at myotube stage in which the activation of p53 showed lesser fusion index value than uninduced cells as well as M3-p53. Reduction of late differentiation marker, Myosin, was confirmed at the protein level. At this stage, p53 and M3-p53 activation shared a similar result in repressing Mef2c, Myogenin, MRF4, and inducing Myf5. These results suggest that p53 or M3-p53 activation leads to delay but not to terminate the differentiation program. Further research would be performing the restoration of Mef2c or Myogenin in excessive activation of p53 or M3-p53 at the myotube formation stage. Expectedly, this strategy could be developed to enhance the differentiation that may have the prospect to cure muscle-related disease. | en_US |