p53 regulates Myogenesis by triggering the differentiation activity of pRb

The p53 oncosuppressor protein regulates cell cycle checkpoints and apoptos is, but increasing evidence also indicates its involvement in differentiati on and development. We had previously demonstrated that in the presence of differentiation-promoting stimuli, p53-defective myoblasts exit from the ce ll cycle but do not differentiate into myocytes and myotubes. To identify t he pathways through which p53 contributes to skeletal muscle differentiatio n, we have analyzed the expression of a series of genes regulated during my ogenesis in parental and dominant-negative p53 (dnp53)-expressing C2C12 myo blasts. We found that in dnp53-expressing C2C12 cells, as well as in p53(-/ -) primary myoblasts, pRb is hypophosphorylated and proliferation stops. Ho wever, these cells do not upregulate pRb and have reduced MyoD activity. Th e transduction of exogenous TP53 or Rb genes in p53-defective myoblasts res cues MyoD activity and differentiation potential, Additionally, in vivo stu dies on the Rb promoter demonstrate that p53 regulates the Rb gene expressi on at transcriptional level through a p53-binding site, Therefore, here we show that p53 regulates myoblast differentiation by means of pRb without af fecting its cell cycle-related functions.