p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress

Cell Death Differ. 2015 Apr;22(4):560-73. doi: 10.1038/cdd.2014.189. Epub 2014 Dec 12.


Acute muscle injury and physiological stress from chronic muscle diseases and aging lead to impairment of skeletal muscle function. This raises the question of whether p53, a cellular stress sensor, regulates muscle tissue repair under stress conditions. By investigating muscle differentiation in the presence of genotoxic stress, we discovered that p53 binds directly to the myogenin promoter and represses transcription of myogenin, a member of the MyoD family of transcription factors that plays a critical role in driving terminal muscle differentiation. This reduction of myogenin protein is observed in G1-arrested cells and leads to decreased expression of late but not early differentiation markers. In response to acute genotoxic stress, p53-mediated repression of myogenin reduces post-mitotic nuclear abnormalities in terminally differentiated cells. This study reveals a mechanistic link previously unknown between p53 and muscle differentiation, and suggests new avenues for managing p53-mediated stress responses in chronic muscle diseases or during muscle aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • MyoD Protein / metabolism
  • Myogenin / chemistry
  • Myogenin / genetics
  • Myogenin / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Cyclin-Dependent Kinase Inhibitor p21
  • MyoD Protein
  • Myogenin
  • Tumor Suppressor Protein p53